The Genetic Epidemiology Network of Arteriopathy (GENOA) was initiated in 1995 to study the genetics of hypertension and its arteriosclerotic complications in sibships. Arteriosclerosis (i.e., atherosclerosis and arteriolosclerosis) of the cardiac, cerebral, renal, and peripheral arteries leads to target organ damage and clinical sequelae such as heart attack, heart failure, stroke, dementia, chronic kidney disease, and claudication. In this application, we propose to conduct an exome-wide association study (Aim 1) and transcriptomic profiling (Aim 2) as cost-effective methods of identifying and studying functional variations in the 1020 GENOA African-American and non-Hispanic White sibships (N=2912) who are at high risk of developing a wide range of arteriosclerotic clinical outcomes. The GENOA cohort provides a unique opportunity to assess the phenotypic impact of rare variants that naturally replicate within a sibship, but may not be seen again even in large epidemiological populations. The GENOA community-based sampling of hypertensive sibships was explicitly designed to study the genetics of multiple late-onset arteriosclerotic diseases that typically become clinically apparent only in the upper generations of families. In order to ultimately identify "at risk" individuals and estimate the cumulative burden of genetic risk allele in two U.S. populations (Aim 3) we will estimate genetic risk scores and assess the attributable fraction of phenotypic variation explained by these new genetic variations.

Public Health Relevance

In this project we will use state-of-the-art exome-wide association study (EWAS) to identify the genetic mutations that make some families have a very high risk of developing heart attacks, strokes, dementia, and kidney disease because of arteriosclerosis.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01HL119443-01A1
Application #
8758883
Study Section
Cardiovascular and Sleep Epidemiology Study Section (CASE)
Program Officer
Jaquish, Cashell E
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109