/ en Thu, 26 Feb 26 09:00:05 -0500 /news/study-reveals-genetic-balancing-act-between-autoimmunity-and-cancer-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Thu, 26 Feb 2026 14:00:05 +0000 jcolaros 5560186 at /news/scientists-sharpen-genetic-maps-help-pinpoint-dna-changes-influence-human-health-traits-and <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Wed, 25 Feb 2026 16:01:27 +0000 tulrich@broadinstitute.org 5560191 at /news/clinical-genomicist-harnesses-team-based-science-help-rare-disease-patients <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Tue, 07 Jan 2025 14:00:00 +0000 adicorat 5557606 at /news/ancient-dna-reveals-possible-origin-racialethnic-disparity-childhood-cancer <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Tue, 26 Mar 2024 18:56:00 +0000 tulrich@broadinstitute.org 5556726 at /news/approach-studies-how-rare-gene-variant-pairs-contribute-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Thu, 07 Dec 2023 17:04:15 +0000 tulrich@broadinstitute.org 5556176 at /news/using-76000-genomes-researchers-build-new-map-regions-human-genome-under-natural-selection <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Thu, 07 Dec 2023 17:00:10 +0000 tulrich@broadinstitute.org 5556181 at /news/new-method-prenatal-genetic-testing-relies-just-blood-draw <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Thu, 23 Nov 2023 14:00:46 +0000 tulrich@broadinstitute.org 5556106 at /news/cellular-atlas-built-guide-precision-treatment-rheumatoid-arthritis <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Tue, 07 Nov 2023 22:33:23 +0000 tulrich@broadinstitute.org 5555981 at /news/whyiscience-qa-computational-biologist-helps-build-datasets-genetic-disease-diagnosis <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Thu, 17 Aug 2023 13:27:18 +0000 Corie Lok 1282671 at /news/nuclear-dna-influences-variation-mitochondrial-dna <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" class="datetime">February 26, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study reveals genetic balancing act between autoimmunity and cancer risk</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-02-26T09:00:05-05:00" title="Thursday, February 26, 2026 - 09:00" class="datetime">February 26, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Cover_Website.png?h=ae0fde30&itok=cdXHmGNE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Cover_Website.png?h=ae0fde30&itok=d0Kt9nPH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Cover_Website.png?h=ae0fde30&itok=DSLvlPO_ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Cover_Website.png?h=ae0fde30&itok=qkC-287e 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Cover_Website.png?h=ae0fde30&itok=OuVjRYvR" alt="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." title="Visualization of shared gene variants related to autoimmunity, cancer, and the thyroid." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Alessio Brioschi, Nicola Cerioli, Mary Pat Reeve, Federico Simeoni, Rupesh Vyas </div> <div class="media-caption__description"> Researchers found more than 400 genetic markers linked to autoimmune hypothyroidism, many of which had distinct biological roles. This graphic sorts genetic signals involved in general autoimmunity (bottom row), cancer (middle), and the thyroid (top). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/597/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/597/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/597/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">An analysis of over 81,000 people with autoimmune hypothyroidism revealed genetic signals specific to the disorder and to thyroid function.</li> <li aria-level="1">Many of the hypothyroid-specific gene variants show a protective effect against skin cancer. </li> <li aria-level="1">The study is consistent with the clinical experience of cancer patients who develop autoimmunity as a side effect of immunotherapy drugs called checkpoint inhibitors. </li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>An autoimmune disorder that affects the thyroid gland, called autoimmune hypothyroidism (AIHT), is the most common autoimmune disease, yet it remains largely understudied. </p> <p>New research from scientists at ӳ����ý, University of Helsinki, and other institutions has found more than 400 genetic markers linked to the disorder, far more than previous studies. Nearly 50 of these pinpoint protein-coding changes in genes involved in immunity and thyroid function.</p> <p>The team discovered that many of the genetic variants that appear to heighten the risk of hypothyroidism may also lower the risk of skin cancer. By performing a genome-wide association analysis of over 81,000 people with AIHT, the scientists were also able to distinguish genetic factors related to thyroid disease from those linked to other autoimmune disorders for the first time. The data they analyzed are from <a target="_blank" href="https://www.finngen.fi/en">FinnGen</a>, the largest medical research project in Finland that utilizes biobank data, and from the UK Biobank. The study is published in <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1"><em>Nature Genetics</em></a>. </p> <p>“This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease,” said study coauthor <a target="_blank" href="/bios/mark-daly">Mark Daly</a>, a ӳ����ý institute member, co-director of ӳ����ý’s Program in <a href="/medical-population-genetics" target="_blank">Medical and Population Genetics</a>, and the founding chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital.  </p> <p>Like all autoimmune diseases, AIHT is caused by the immune system mistakenly attacking healthy tissue in the body — in this case, the thyroid gland, and as a result it lowers the production of thyroid hormones, which help regulate metabolism. But why does an autoimmune disease attack only certain cells and tissues, and what are the underlying mechanisms? These questions prompted the team to look deeper into the genetic basis of AIHT.</p> <p>"Hypothyroidism affects millions of people, predominantly women, and yet the biology underlying it has remained largely unexplored," said study lead author Mary Pat Reeve, a data scientist at ӳ����ý and doctoral researcher at the Institute for Molecular Medicine Finland (FIMM) of the University of Helsinki. "Conditions like this one are scientifically rich precisely because they sit at the intersection of immunity, organ function, and metabolism. By bringing together over 81,000 cases, we had the statistical power to separate the genetics of autoimmunity from thyroid function — and that separation revealed a connection to cancer risk that opens a window onto fundamental mechanisms of immune regulation that matter far beyond thyroid disease."</p> <p><strong>Cancer - autoimmunity connection </strong></p> <p>Reeve and her colleagues found that many of the AIHT genetic factors have distinct biological roles. For example, 38 percent of them are involved in general autoimmunity, while 20 percent are thyroid-organ specific. </p> <p>Additionally, 10 percent of the genetic signals show a protective effect against skin cancer. Some of those genes encode checkpoint proteins, which act as brakes on the immune system to prevent it from attacking healthy tissue. This finding suggests a genetic link between increased autoimmunity risk and decreased cancer risk: gene variants associated with reduced checkpoint activity can lead to a stronger immune attack against both cancer cells and healthy tissue alike. </p> <p>Checkpoint proteins are targeted by a class of cancer immunotherapy drugs called checkpoint inhibitors, which release the brakes on the immune system so that it can better attack cancer cells. Some cancer patients who respond well to these medicines experience hypothyroidism as a side effect, and Daly says the study offers a possible genetic explanation for why.</p> <p>“Our work is consistent with the clinical experience of patients who develop autoimmunity as a side effect of checkpoint inhibitors, and it’s often those same patients who have better cancer outcomes,” Daly said.</p> <p>Reeve added that the study supports the idea that cancer and autoimmunity risk differ from person to person because of genetic differences. As a next step, the team is working to uncover how these genetic variants contribute to distinct components of a disease, to then eventually find ways to intervene. </p> <p>“This project is an example of the value of the deep, longitudinal clinical phenotypes available in FinnGen, enabling the discovery of connections and shared biology across a wide range of diseases while using genetic profiles as causal anchors. A long-term partnership between FIMM and the ӳ����ý has made these genetic discoveries possible,” said senior author <a target="_blank" href="https://www.helsinki.fi/en/researchgroups/complex-disease-genetics/people">Samuli Ripatti</a>, director of FIMM, professor of biometry at the University of Helsinki, and affiliated faculty at ӳ����ý and Massachusetts General Hospital. </p> <p>Author <a target="_blank" href="/bios/ramnik-xavier">Ramnik Xavier</a>, a ӳ����ý core institute member, the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, and director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, added that ӳ����ý and FinnGen investigators have initiated studies to determine how these variants contribute to disease using human organoid models. “Population genetics is a uniquely powerful approach to discover fundamental mechanisms of immune regulation that govern organ specific and systemic autoimmunity,” Xavier said. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This research was supported by U.S. National Institutes of Health, Sigrid Juselius Foundation, the Academy of Finland Center of Excellence in Complex Disease Genetics, the Academy of Finland, and the University of Helsinki.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Reeve, et al. <a target="_blank" href="https://www.nature.com/articles/s41588-026-02521-1">Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk</a>. <em>Nature Genetics</em>. Online February 26, 2026. DOI: 10.1038/s41588-026-02521-1 <br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> </div> </div> </div> </div> </div> Wed, 16 Aug 2023 15:00:00 +0000 adicorat 1282596 at