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For researchers on the hunt for the genetic roots of disease, the cost of deep whole-genome sequencing makes it challenging to conduct large genetic studies involving thousands of participants, which are needed to reveal new genetic insights. So scientists at the ӳ����ý came up with a clever approach, called the , that lowers the cost of sequencing by 75 percent and is becoming one of the most commonly used sequencing methods at the ӳ����ý.

Now those researchers have published the first scientific paper describing BGE’s utility, showing that the method generates high-quality data at a much lower cost than the current gold-standard of deep whole-genome sequencing. The study, in , is from scientists in the Stanley Center for Psychiatric Research at the ӳ����ý and .

“In this study, we’ve shown that the BGE technology works and it works at scale, and now the entire field can benefit from the method,” said co-senior author Alicia Martin, a ӳ����ý associate member, an assistant investigator in the Analytic and Translational Genetics Unit of Massachusetts General Hospital, and an assistant professor at Harvard Medical School.

Many researchers have already benefited from BGE. Since ӳ����ý Clinical Labs first began offering BGE in late 2022, they have used the low-cost method to sequence more than 400,000 human DNA samples from dozens of research studies. In 2025 alone, ӳ����ý Clinical Labs processed nearly 123,000 samples using the BGE method, representing 30 percent of all genomic specimens processed that year.

The method allows scientists to conduct larger studies, to better survey variation in ancestrally diverse populations, and to accelerate new genetic discoveries on the roots of human disease. A version of the method designed for clinical use is now enabling low-cost genetic testing for patients, including those at risk of prostate cancer.

Balancing the blend

The idea for BGE was born from a need to cost-effectively analyze thousands of genomes. “In the Stanley Center, we want to identify the heritable basis of severe mental illnesses, and doing so requires very large sample sizes,” said Martin, who led the new work along with ӳ����ý core faculty member Ben Neale and Dan Howrigan, a group leader in the Stanley Center. “To reach the scale that we need, with a fixed budget, we need to be able to ideally capture as much of the genome as we can, but at the lowest cost possible.”

BGE takes two complementary scans of the genome that together give a full view of how it varies among people. One scan includes deep coverage of the exome, or the protein-coding parts of the genome that tend to harbor rare, high-impact mutations. The other lighter scan looks across the entire genome, capturing the many common genetic variants that influence traits and risk for common disease.

In the new study, the researchers describe how they developed BGE and demonstrate its utility by applying it to more than 53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) project, which includes people from African, African American, and Latin American populations.

They found that BGE measured far more variants than possible with genotyping arrays, which read only specific locations in the genome. And BGE did this at roughly a quarter of the cost of using deep-coverage whole genome sequencing.

In addition to being lower cost and unbiased, BGE can also measure structural variants — extra or missing bits of DNA — that are known to underlie some psychiatric conditions. Another advantage of BGE is that the genome and exome data are generated in a single run on the sequencing machine, so data are already synchronized, avoiding problems faced when combining data created separately.

By helping uncover more disease-causing variants, the method could lead to polygenic scores that better predict an individual’s risk of disease, especially for groups poorly represented in genomics research today. “Studying a more broad and diverse set of participants allows us to identify new potential biologies, find novel loci associated with severe mental illnesses, and better understand the roles of variants that we do uncover,” Martin said.

The researchers are grateful for the participants who may not only benefit one day from this work, but who make it possible. “We're incredibly appreciative of their willingness to share their DNA, particularly when many of them have some of these disorders that are pretty stigmatized in different ways around the world,” said Martin.