Ó³»­´«Ã½

At the root of most common diseases in modern society is a confusing mix of confounding factors, including genes, lifestyle, and the environment. Now, thanks to a grant of more than $18M from the National Heart, Lung, and Blood Institute (NHLBI), Ó³»­´«Ã½ scientists will be major contributors to a landmark effort to identify the genetic differences among humans that underlie such frequent diseases. This work will result in an open data resource for the entire biomedical community that combines genetic analyses with detailed information about disease characteristics, allowing researchers to make key scientific links between human genetic variability and disease.

Known as the Candidate gene Association Resource, or CARe, this 4-year project involves a close scrutiny of the DNA of thousands of individuals — some 50,000 in total — who are enrolled in NHLBI studies that focus on heart, lung, blood and sleep disorders. Stacey Gabriel, the director of the Genetic Analysis Platform and the National Center for Genotyping and Analysis at the Ó³»­´«Ã½, and Joel Hirschhorn, an associate member of the Ó³»­´«Ã½ and coordinator of its Metabolic Disease Initiative, will lead scientists in cataloguing the genetic differences contained in specified "candidate genes" of interest, that is, genes identified as likely sources of inherited variation that are most relevant for disease.

"The research funded by this award should result in new insights into how genetic variation contributes to health and disease," said Gabriel. "We will work together with other members of the CARe network to combine new methods for measuring genetic variation with an unprecedented collection of large, well-characterized clinical cohorts."

"The sheer scale of this project with genetic data collected from as many as 50,000 participants allows for more in-depth analyses of diseases across multiple races and ethnicities," said NHLBI Director Elizabeth G. Nabel. "The database will be a tremendous resource for scientists — speeding identification of risk factors and genetic variants associated with disease and disorders."

The scientists will record small differences in DNA sequence, known as single nucleotide polymorphisms ("SNPs"), in more than 1,700 candidate genes drawn from the individuals in NHLBI disease cohorts. Advanced bioinformatic methods will enable researchers to correlate these findings with the observed features of disease, allowing them to estimate the frequency of a particular SNP in the overall population, to predict the level of disease risk that it confers, and to approximate the degree to which it contributes to the severity of a particular disease. Ó³»­´«Ã½ scientists David Altshuler, Mark Daly, Sekar Kathiresan, and Chris Newton-Cheh will contribute to this groundbreaking effort. Its computational arm will be led by Marcia Nizzari, the director of informatics development for the Ó³»­´«Ã½'s Medical and Population Genetics Program.

"By applying new, cutting-edge genetic, genomic and statistical methods to cohorts collected by NHLBI-funded investigators, we will definitively test the most promising genes for association with many important diseases and pre-disease states," said Hirschhorn. "The discoveries that stem from this work will enlighten us as to why some people become ill and others remain healthy, and can help focus future efforts to develop improved disease therapies and preventive measures."