human lung anatomy

Economic stimulus fuels NIH search for genetic disease signatures

Today, the National Heart, Lung, and Blood Institute (NHLBI), one of the National Institutes of Health, announced a "Grand Opportunity" Large-Scale DNA Sequencing Project that will spend more than $64 million over two years to identify genetic connections to heart, lung, and blood diseases that account for three of the four leading causes of death in the United States.

The NHLBI Large-Scale DNA Sequencing Project, made possible by the American Recovery and Reinvestment Act of 2009 (Recovery Act), is the NHLBI's largest, single capital investment of the $750 million NHLBI Recovery Act expenditure, and has been deemed a "signature" co-funded project by the NIH Office of the Director.

Six awards will fund researchers at five academic institutions to work together to launch a landmark DNA sequencing and molecular profiling project that will mine genetic information from years of informative clinical data gathered from population studies investigating heart, lung and blood diseases. The NHLBI Large-Scale DNA Sequencing Project will support the following principal investigators over a two-year period:

  • Deborah Nickerson, Ph.D., University of Washington, Seattle ($25 million to serve as a Sequencing Center)
  • Stacey Gabriel, Ph.D., Broad Institute of MIT and Harvard, Cambridge, Massachusetts ($25 million to serve as a second Sequencing Center)
  • Rebecca D. Jackson, M.D., Ohio State University Medical Center, Columbus, Ohio ($4.5 million to manage the contributions of the Women's Health Initiative cohort)
  • Michael J. Bamshad, M.D., University of Washington, Seattle ($5.2 million to manage the NHLBI lung cohorts)
  • Timothy A. Graubert, M.D., Washington University, St. Louis, Missouri ($2.5 million to manage data from patients with myelodysplastic syndrome)
  • Stephen S. Rich, Ph.D., University of Virginia Health System, Charlottesville, Virginia ($2.3 million to coordinate data from six NHLBI cohorts)

The NHLBI has recorded years of detailed information about the outward signs or characteristics – known as phenotypes – of various heart, lung and blood diseases. During the course of these studies, scientists have obtained permission from study participants to collect their DNA. Genomic technologies have advanced to the point where scientists can rapidly and efficiently – yet very precisely – analyze DNA from these population studies that have tracked health outcomes in genetically and ethnically diverse groups.

Billions of DNA sequences from more than 8,000 people who participated in these long-term studies will be analyzed to find genetic contributors to heart, lung and blood diseases. By the end of the project, all data will be deposited in an NIH database available to the scientific community, prompting a significant multiplier effect toward medical discovery.

Genome-wide scanning methods, or GWAS, have provided tantalizing hints about the genetic causes and contributors to phenotypes that typify heart attack, stroke, diabetes, obesity, hypertension, asthma, chronic pulmonary disease, and pre-cancerous blood disorders such as myelodysplastic syndrome, which killed astronomer Carl Sagan and children's author Roald Dahl. But these "fly-over" genome-scanning approaches have not provided enough detail to assign a particular gene or genes to various phenotypes: the propensity for having a heart attack under the age of 50, for example, the sensitivity to particular environmental irritants that trigger asthma, or whether or not someone with myelodysplastic syndrome will get leukemia.

The NHLBI Large-Scale DNA Sequencing Project greatly enhances the opportunity for researchers to discover specific genetic variants that map precisely with disease phenotypes by enabling them to scour thousands of DNA sequences in extremely fine detail. The NHLBI Large-Scale DNA Sequencing Project investment is a key component of the larger NIH Recovery Act DNA sequencing investment, which in total will analyze all or part of 34,000 human genomes to find genes linked not just to heart, lung, and blood diseases, but also to cancer and autism.

Historically, such a "deep" sequencing effort would be prohibitively time-consuming, costly and laborious for a single laboratory. However, advances in sequencing technology coupled with the infusion of Recovery Act funds will recruit and employ hundreds of researchers to work together over the next two years to accomplish this vital step in the path toward achieving personalized medicine.

When analyzing the cohort-based genomes, the scientists will use a cutting-edge, selective approach called exome sequencing. This involves identifying and sequencing the genetic alphabet of only those genes that make proteins. Called exons, these important parts of the human genome make up only one percent of all of human DNA.

Through the NHLBI funding, exome sequencing was pioneered this year by one of the NHLBI Large-Scale DNA Sequencing Project’s principal investigators, Deborah Nickerson, Ph.D., and her colleagues at the University of Washington in Seattle. It is being hailed as an efficient way to enrich the findings revealed from previous GWAS experiments, accelerating the search for unambiguous genetic links to disease.

Previous studies have documented that genomic factors predict the severity of heart disease as well as lung and blood disorders such as asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary arterial hypertension, cystic fibrosis and myelodysplastic syndrome, a blood disorder that often progresses to leukemia. NHLBI Large-Scale DNA Sequencing Project scientists will also search for genetic signatures of myelodysplastic syndrome in data from patients with the condition.

The NHLBI Large-Scale DNA Sequencing Project team will analyze genomic information from the following well-phenotyped heart and lung cohorts:

  • Women's Health Initiative (WHI)
  • Atherosclerosis Risk in Communities (ARIC)
  • Coronary Artery Risk Development in Young Adults (CARDIA)
  • Cardiovascular Health Study (CHS)
  • Jackson Heart Study (JHS)
  • Multi-Ethnic Study of Atherosclerosis (MESA)
  • Framingham Heart Study (FHS)
  • Genomic Research on Asthma in the African Diaspora (GRAAD)
  • Lung Health Study (LHS)
  • Pulmonary Arterial Hypertension (PAH) population
  • Acute Lung Injury (ALI) cohort
  • Cystic fibrosis (CF) cohort

NHLBI Communications Office:

Backgrounder: NHLBI Large-Scale DNA Sequencing Project population studies

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at

The National Institutes of Health — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit



Last Updated September 30, 2009