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- Study Description
This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, one called Freeze 4 (GRCh37) and another called Freeze 5b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 4, Phase 1" and "TOPMed Whole Genome Sequencing Project - Freeze 5b, Phases 1 and 2". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.
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. Only participants of the African-American Cohort were sequenced through TOPMed.
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.
Comprehensive phenotypic data for GENOA study participants are available through dbGaP phs001238.
- Authorized Access
- Publicly Available Data (Public ftp)
Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.
- Study Inclusion/Exclusion Criteria
Selection into GENOA
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.
Selection into TOPMed
Every participant with an echocardiogram was selected for WGS. We then selected 106 participants who had a computed tomography scan for coronary artery calcification but not an echocardiogram or were a sibling of someone already selected for WGS. Finally, we excluded individuals whom we knew were already being whole genome sequenced through TOPMed or another sequencing effort (GENOA participants who overlap with ARIC or JHS participants). GENOA has phenotypes and omic data for these overlapping participants.
- Molecular Data
Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Whole Genome Sequencing Illumina HiSeq X Ten N/A N/A Sequencing was performed at the Northwest Genomics Center at the University of Washington for the HyperGen/GENOA project (PI: Donna Arnett) and the Broad Institute of MIT and Harvard for the AA-CAC project (PI: Kent Taylor)
- Study History
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.
- Selected publications
- Diseases/Traits Related to Study (MESH terms)
- Primary Phenotype: Hypertension
- Arterial Pressure
- Blood Pressure
- Cardiovascular Diseases
- Cholesterol, HDL
- Cholesterol, LDL
- Coronary Artery Disease
- Diabetes Mellitus
- Hypertrophy, Left Ventricular
- Kidney Failure, Chronic
- Obesity, Abdominal
- Peripheral Arterial Disease
- Renal Insufficiency, Chronic
- Vascular Calcification
- Links to Related Resources
- Authorized Data Access Requests
- Study Attribution