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Backgrounder: NHLBI Large-Scale DNA Sequencing Project population studies

The $63 million NHLBI Large-Scale DNA Sequencing Project is a "Grand Opportunity" Recovery Act project that will find genetic signatures for heart, lung, and blood diseases that account for 3 of the 4 leading causes of death in the United States. President Barack Obama announced the award September 30, 2009, as part of the $5 billion in new scientific research that is being underwritten by funds from the $787 billion American Recovery and Reinvestment Act.

What DNA will be Sequenced?

A team of researchers across the United States will meticulously analyze the DNA of more than 8,000 people that has been gathered from both individual patients and population studies investigating heart, lung and blood diseases.

Why Population Studies?

Population studies, often called cohort studies, have carefully tracked health outcomes in large, genetically and ethnically diverse groups of people over many years. The NHLBI has obtained permission to collect and analyze DNA from these studies. These gold mines of health information will help researchers uncover genetic variants that align with observable traits of health and disease.

What are the Studies?

The NHLBI has long been a leader in conducting population studies for heart, lung, and blood diseases. The Large-Scale DNA Sequencing Project continues this tradition by directing multiple population studies and participant samples through two sequencing centers to streamline data analysis and avoid repetition. The results will be publicly accessible. The studies that will be examined as part of this project comprise cardiovascular disease, lung disease, myelodysplastic disorders, women's health, and a consortium encompassing heart, lung, and blood disease. They are listed below.

Cardiovascular Disease Population Studies

"Human Exome Sequencing in Six Well-Phenotyped NHLBI Cohorts"
Stephen Rich, Ph.D., University of Virginia, Charlottesville

1. Atherosclerosis Risk in Communities (ARIC) Study

  • Start of Exams: 1987
  • Focus: Development and progression of atherosclerosis in the community
  • Number of Participants: 15,792
  • Age Range: 45-64
  • Ethnicity: 25 percent African American
  • Locations: Forsyth Co, N.C.; Jackson, Miss.; Minneapolis, Minn.; and Washington Co, Md.

2. Cardiovascular Heart Study (CHS)

  • Start of Exams: 1989
  • Focus: Development and progression of clinical cardiovascular disease in older adults
  • Number of Participants: 5,888+
  • Age Range: 65+
  • Ethnicity: 16 percent African American
  • Locations: Forsyth Co, N.C.; Pittsburgh; Sacramento, Calif.; Washington Co, Md.

3. Multi-Ethnic Study of Atherosclerosis (MESA)

  • Start of Exams: 2000
  • Focus: Factors that relate to the progression of subclinical cardiovascular disease
  • Number of Participants: 6,814
  • Age Range: 45-84
  • Ethnicity: 28 percent African American, 22 percent Latin American, 12 percent Chinese American
  • Locations: New York; Baltimore; Forsyth Co, N.C.; Chicago; St. Paul, Minn.; and Los Angeles

4. Coronary Artery Risk Development in Young Adults (CARDIA)

  • Start of Exams: 1985
  • Focus On: Development and progression of risk factors in young adults
  • Number of Participants: 5,115
  • Age Range: 18-30
  • Ethnicity: 52 percent African American
  • Locations: Birmingham, Ala.; Chicago; Minneapolis, Minn.; and Oakland, Calif.

5. Jackson Heart Study (JHS)

  • The largest single-site, prospective, epidemiologic investigation of cardiovascular disease among African Americans ever undertaken
  • Spin-off of the ARIC study
  • Start of Exams: 2000
  • Focus: Risk factors for hypertension, coronary heart disease, stroke, peripheral arterial disease, heart failure, and renal disease in African Americans
  • Number of Participants: 5,302
  • Age Range: 21+
  • Ethnicity: 100 percent African American
  • Location: Jackson, Miss. and surrounding counties

Each study described above surveyed equal numbers of men and women.


Lung Disease Population Studies

"ARRA – NHLBI Lung Cohorts Sequencing Project"
Michael Bamshad, M.D., University of Washington, Seattle

1. Genomic Research on Asthma in the African Diaspora (GRAAD)

  • Focus: Physician-diagnosed asthma, presence of hallmark symptoms, and asthma medication use
  • Ethnicity: African Caribbean asthmatics and their families from Barbados; African American asthma cases and non-asthmatic controls

2. Lung Health Study (LHS)

  • Landmark study; ten-center clinical trial
  • Focus: Understanding the effects of smoking and whether a smoking intervention program and an inhaled bronchodilator could slow the decline of pulmonary function in participants with Chronic Obstructive Pulmonary Disease (COPD) in the short- and long term

3. Molecular Determinants of Pulmonary Arterial Hypertension (PAH) Study

  • Patients with idiopathic (unknown cause) pulmonary arterial hypertension (increased pressure in the arteries of the lungs), and patients with PAH and scleroderma (skin hardening)
  • Focus: Uses physiological, molecular, genomic and proteomic approaches and phenotyping instrumentation to understand pulmonary vascular (PV) and right ventricular remodeling and their impact on PAH morbidity and mortality

4. Acute Lung Injury (ALI)

  • Cohort 1:
    • Number of patients: ~950
    • Focus: Critically ill patients with systemic inflammatory responses syndrome (SIRS), followed through their ICU and hospital stay until death or discharge from the hospital
    • Location: Harborview Medical Center
  • Cohort 2:
    • Number of patients: ~1,800
    • Focus: Trauma patients who were at risk for acute lung injury

5. Cystic fibrosis (CF)

  • Cohort 1:
    • Number of patients: 1,704
    • Focus: Participants drawn from the Early Pseudomonas Infection Control (EPIC) Observational Study, the world’s largest, multicenter, longitudinal, prospective cohort of early lung disease in young CF patients.
  • Cohort 2:
    • Number of patients: 1,208
    • Focus: Studying lung function over five years for patients at the extremes of lung disease severity ("severe" in worst 25th percentile of birth cohort vs. "mild" in best 25th percentile)


Blood Disorders

"Whole Genome Sequencing of Myelodysplastic Syndromes"*
Timothy Graubert, M.D., Washington University, St. Louis, Mo.

* Myelodysplastic syndrome is a poorly understood set of diseases of the blood. It used to be known as "pre-leukemia" because it can lead to that type of blood cancer. Because it is relatively rare, large population studies are not possible. Thus, Dr. Graubert’s team will use a method called whole-genome sequencing to analyze the DNA from the cells of patients who have this disorder. All the work will be done at the Genome Center at Washington University, St. Louis, Mo.


Women's Health Population Studies

"WHI Sequencing Project (WHISP)"
Rebecca Jackson, M.D., Ohio State University Medical Center, Columbus

Women's Health Initiative Observational Study

  • Number of Participants: 93,676
  • Age Range: 50-79 (postmenopausal)


Heart, Lung, and Blood Consortium

Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

The CHARGE consortium is an ongoing study--a "group of groups"--that will re-analyze genome-wide association study (GWAS) data from several population-based studies. By pooling data from many studies, the scientists hope to uncover genetic signatures for heart, lung, and blood diseases.

CHARGE is a team effort between NIH, several universities, and other research organizations that consists of five participating population studies (cohorts):

  • Age, Gene/Environment, Susceptibility--Reykjavik (AGES)
  • Atherosclerosis Risk in Communities Study (ARIC)
  • Cardiovascular Health Study (CHS)
  • Framingham Heart Study (FHS)
  • Rotterdam Study


Last Updated February 2, 2010