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)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL119443-02
Application #
8918019
Study Section
Cardiovascular and Sleep Epidemiology Study Section (CASE)
Program Officer
Jaquish, Cashell E
Project Start
2014-09-01
Project End
2018-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Ward-Caviness, Cavin K; Huffman, Jennifer E; Everett, Karl et al. (2018) DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis. Blood 132:1842-1850
Liu, Jiaxuan; Zhao, Wei; Ware, Erin B et al. (2018) DNA methylation in the APOE genomic region is associated with cognitive function in African Americans. BMC Med Genomics 11:43
Kattah, Andrea G; Suarez, Maria L G; Milic, Natasa et al. (2018) Hormone therapy and urine protein excretion: a multiracial cohort study, systematic review, and meta-analysis. Menopause 25:625-634
Rudra, Pratyaydipta; Broadaway, K Alaine; Ware, Erin B et al. (2018) Testing cross-phenotype effects of rare variants in longitudinal studies of complex traits. Genet Epidemiol 42:320-332
Wright, Michelle L; Ware, Erin B; Smith, Jennifer A et al. (2018) Joint Influence of SNPs and DNA Methylation on Lipids in African Americans From Hypertensive Sibships. Biol Res Nurs 20:161-167
Ben-Avraham, Dan; Karasik, David; Verghese, Joe et al. (2017) The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY) 9:209-246
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Chu, Audrey Y; Deng, Xuan; Fisher, Virginia A et al. (2017) Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation. Nat Genet 49:125-130
Nandakumar, Priyanka; Lee, Dongwon; Richard, Melissa A et al. (2017) Rare coding variants associated with blood pressure variation in 15?914 individuals of African ancestry. J Hypertens 35:1381-1389
Canales, Benjamin K; Smith, Jennifer A; Weiner, I David et al. (2017) Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH. Kidney Int Rep 2:1111-1121

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