Genetic Epidemiology Network of Arteriopathy (GENOA)

The Genetic Epidemiology Network of Arteriopathy (GENOA) is one of four networks in the NHLBI Family-Blood Pressure Program (FBPP). GENOA's long-term objective is to elucidate the genetics of target organ complications of hypertension, including both atherosclerotic and arteriolosclerotic complications involving the heart, brain, kidneys, and peripheral arteries. The longitudinal GENOA Study recruited European-American and African-American sibships with at least 2 individuals with clinically diagnosed essential hypertension before age 60 years. All other members of the sibship were invited to participate regardless of their hypertension status. Participants were diagnosed with hypertension if they had either 1) a previous clinical diagnosis of hypertension by a physician with current anti-hypertensive treatment, or 2) an average systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg based on the second and third readings at the time of their clinic visit.

The Family Blood Pressure Program (FBPP), GENOA's parent program, is an unprecedented collaboration to identify genes influencing blood pressure (BP) levels, hypertension, and its target-organ damage. This program has conducted over 21,000 physical examinations, assembled a shared database of several hundred BP and hypertension-related phenotypic measurements, completed genome-wide linkage analyses for BP, hypertension, and hypertension associated risk factors and complications, and published over 130 manuscripts on program findings. The FBPP emerged from what was initially funded as four independent networks of investigators (HyperGEN, GenNet, SAPPHIRe and GENOA) competing to identify genetic determinants of hypertension in multiple ethnic groups. Realizing the greater likelihood of success through collaboration, the investigators created a single confederation with program-wide and network-specific goals.

• Study Weblinks:
  • FBPP
  • STAMPEED
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Sibling Cohort
• Total number of consented subjects: 3462
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

At least two siblings in each sibship needed to have essential hypertension diagnosed prior to age 60 years of age, defined as: 1) average of the last 2 out of 3 systolic BP readings ≥ 140mmHg, or 2) an average of the last 2 out of 3 diastolic BP readings ≥ 90 mmHg, or 3) previous diagnosis of hypertension and antihypertensive medication prescribed by a physician to be taken daily during the last month.

The definition of essential hypertension excluded those with diagnosis of hypertension ≥ 60 yrs of age, or secondary causes of hypertension including but not limited to prior knowledge of renal parenchymal disease or serum creatinine ≥ 2.5 mg/dL, renal vascular disease, primary aldosteronism, pheochromocytoma, coarctation of aorta, hypertension associated with current use of oral contraceptive agents, prescription or non-prescription drugs, or active alcohol abuse.

Exclusion criteria for all participants included secondary hypertension, alcoholism or drug abuse, pregnancy, breast feeding, and type I diabetes mellitus (juvenile onset, insulin dependent) or active malignancy.

During the first exam (Phase 1; 1996-2000), 1,583 European-Americans from Rochester, MN and 1,854 African-Americans from Jackson, MS were examined. Between 2000 and 2004 (Phase 2), 1,241 participants of the European-American Cohort and 1,482 participants of the African-American cohort returned for a second examination. The second examination of the European-American cohort included computed tomography scans for coronary artery calcification while the second examination of the African-American cohort included an echocardiogram. During this time period, an MRI of the brain was obtained through the Genetics of Microangiopathic Brian Injury (GMBI) Study. Between 2007 and 2009, an examination that focused on measures of renal disease (CKD Study) was conducted on 625 participants of the European-American cohort and 611 participants of the African-American cohort. Between 2009 and 2011, an examination that included computed tomography scans for coronary artery calcification (CAC Study) was conducted on 752 participants of the African-American Cohort.

Name of grant: Genetic Mechanisms of Arteriosclerosis in Hypertensive Sibships
Agency number: NIH, NHLBI, R01 HL119443
PI: Sharon LR Kardia, PhD
Dates: 2014-2018
Specific aims: To use existing exome variant data plus 1000 Genomes data and transcriptomic profiling to identify and study functional variations in the genome in GENOA European-American and African-American sibships.
Cohort: European-Americans, African-Americans

Name of grant: Predictors of Coronary Artery Calcification in an African-American Cohort (CAC Study)
Agency number: NIH, NHLBI, R01 HL085571
PI: Patricia A Peyser, PhD
Dates: 2007-2011
Specific aims: Assess coronary artery calcification quantity in African-American siblings from the GENOA Field Center in Jackson, MS and localize genes influencing coronary artery calcification quantity.
Cohort: African-Americans

Name of grant: Genomic Predictors of Arteriosclerosis in Hypertensives
Agency number: NIH, NHLBI, R01 HL087660
PI: Sharon LR Kardia, PhD
Dates: 2007-2010
Specific aims: Conduct genome-wide association study of phenotypic measures of arteriosclerosis and investigate the role of context dependent genetic effects on the distribution of target organ disease.
Cohort: European-Americans, African-Americans

Name of grant: Genetics of Chronic Kidney Disease (CKD Study)
Agency number: NIH, NIDDK, R01 DK073537
PI: Stephen T Turner, MD
Dates: 2006-2010
Specific aims: Identify genetic predictors of chronic kidney disease in previously well-characterized European-American and African-American sibships with 2 or more hypertensive members.
Cohort: European-Americans, African-Americans

Name of grant: Genetics of Microangiopathic Brian Injury (GMBI)
Agency number: NIH, NINDS, R01 NS041558
PI: Stephen T Turner, MD
Dates: 2001-2005 and 2009-2010
Specific aims: Identify genes contributing to ischemic damage to the subcortical white matter of the brain, referred to as leukoaraiosis.
Cohort: European-Americans, African-Americans

Name of grant: NHLBI Family Blood Pressure Program (Phase 2)
Agency number: NIH, NHLBI, U10 HL054464
PI: Stephen T Turner, MD
Dates: 2000-2004
Specific aims: To identify genes influencing blood pressure levels, hypertension and its target-organ damage.
Cohort: European-Americans, African-Americans

Name of grant: Genetic Determinants of High BP in Three Racial Groups (Phase 1)
Agency number: NIH, NHLBI, U10 HL054464
PI: Stephen T Turner, MD
Dates: 1995-1999
Specific aims: To identify genes influencing blood pressure levels, hypertension and its target-organ damage.
Cohort: European-Americans, African-Americans

Name of grant: Genetic Determinants of High BP in Three Racial Groups (Phase 1)
Agency number: NIH, NHLBI, U10 HL054457
PI: Charles Sing, PhD (1995-1999); Sharon LR Kardia PhD (2000-2004)
Dates: 1995-2004
Specific aims: To identify genes influencing blood pressure levels, hypertension and its target-organ damage.
Cohort: European-Americans, African-Americans

Name of grant: Genetic Determinants of High BP in Three Racial Groups (1995-2004) / The Family Blood Pressure Program (GENOA Network) (2005-2007) (Phase 1 and Phase 2)
Agency number: NIH, NHLBI, U10 HL054481
PI: Eric Boerwinkle, PhD
Dates: 1995-2007
Specific aims: To identify genes influencing blood pressure levels, hypertension and its target-organ damage.
Cohort: European-Americans, African-Americans

• Primary Phenotype: Hypertension
• Aging
• Arterial Pressure
• Arteriosclerosis
• Atherosclerosis
• Biomarkers
• Blood Pressure
• Cardiovascular Diseases
• Cholesterol
• Cholesterol, HDL
• Cholesterol, LDL
• Coronary Artery Disease
• Diabetes Mellitus
• Echocardiography
• Endophenotypes
• Hyperglycemia
• Hyperinsulinism
• Hypertrophy, Left Ventricular
• Inflammation
• Kidney Failure, Chronic
• Leukoaraiosis
• Lipids
• Obesity
• Obesity, Abdominal
• Peripheral Arterial Disease
• Renal Insufficiency, Chronic
• Triglycerides
• Vascular Calcification

• Principal Investigators
  • Sharon Kardia, PhD. University of Michigan, Ann Arbor, MI, USA.
  • Eric Boerwinkle, PhD. University of Texas Health Science Center, Houston, TX, USA.
  • Stephen T. Turner, MD. Mayo Clinic, Rochester, MN, USA.
  • Thomas H. Mosley, Jr, PhD. University of Mississippi Medical Center, Jackson, MS, USA.
  • Patricia A. Peyser, PhD. University of Michigan, Ann Arbor, MI, USA.
• Co-Investigators
  • Jennifer A. Smith, PhD. University of Michigan, Ann Arbor, MI, USA.
  • Lawrence F. Bielak, DDS, MPH. University of Michigan, Ann Arbor, MI, USA.
• Funding Sources
  • National Institutes of Health, Bethesda, MD, USA.