Hypertension is a leading cause of global disease burden, mortality and disability, contributing to a greater risk of cardiovascular disease, stroke and chronic kidney disease. African Americans are disproportionally affected by hypertension and its complications. Whether these racial/ethnic differences in hypertension risk are related to genetic factors is currently unknown. Studies of individuals of diverse ancestry have provided evidence for presence of additional common variants in the population with broad effects across ancestries, which could be leveraged for gene discovery in trans-ethnic meta-analysis. Using genome wide association study data from the COGENT-BP and CHARGE-BP consortia, we propose to perform trans-ethnic meta-analyses of blood pressure traits in individuals of African and European ancestry for variant discovery and fine mapping of loci, by leveraging trans-ethnic differences in allele frequencies and the patterns of linkage disequilibrium. We will examine the evidence for association of the most significantly associated blood pressure variants with clinical relevant cardiovascular disease and kidney outcomes in collaborations with established consortia. Findings from this study could have a broad impact on gene discovery and fine mapping of loci, and may provide information on genetic determinants of racial/ethnic disparities to guide strategies for prevention and treatment of hypertension and its complications.

Public Health Relevance

High blood pressure is a leading cause of global disease burden, mortality and disability, contributing to a greater risk of coronary heart disease, stroke and chronic kidney disease. Identification of genetic factors influencing inter-individual variance in blood pressure can provide insights to the development of drug targets and ultimately be used to reduce the burden of hypertension and its complications.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL123677-01
Application #
8755381
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wright, Jacqueline
Project Start
2014-09-01
Project End
2016-05-30
Budget Start
2014-09-01
Budget End
2015-05-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Franceschini, Nora; Giambartolomei, Claudia; de Vries, Paul S et al. (2018) GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nat Commun 9:5141
M├Ągi, Reedik; Horikoshi, Momoko; Sofer, Tamar et al. (2017) Trans-ethnic meta-regression of genome-wide association studies accounting for ancestry increases power for discovery and improves fine-mapping resolution. Hum Mol Genet 26:3639-3650
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Sofer, Tamar; Baier, Leslie J; Browning, Sharon R et al. (2017) Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits. PLoS One 12:e0188400
Howson, Joanna M M; Zhao, Wei; Barnes, Daniel R et al. (2017) Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet 49:1113-1119

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