Genetic ancestry,population sub-structure,and cardiovascular disease-related traits among African-American participants in the CARDIA Study |
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Authors: | Alexander P Reiner Christopher S Carlson Elad Ziv Carlos Iribarren Cashell E Jaquish Deborah A Nickerson |
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Institution: | (1) Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195, USA;(2) Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA;(3) Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA;(4) Kaiser Permanente Division of Research, Oakland, CA, USA;(5) National Heart, Lung, and Blood Institute (NHLBI), Bethesda, USA;(6) Department of Genome Sciences and Bioengineering, University of Washington, Seattle, WA 98195, USA |
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Abstract: | African-American populations are genetically admixed. Studies performed among unrelated individuals from ethnically admixed
populations may be both vulnerable to confounding by population stratification, but offer an opportunity for efficiently mapping
complex traits through admixture linkage disequilibrium. By typing 42 ancestry-informative markers and estimating genetic
ancestry, we assessed genetic admixture and heterogeneity among African-American participants in the Coronary Artery Risk
Development in Young Adults (CARDIA) cohort. We also assessed associations between individual genetic ancestry and several
quantitative and binary traits related to cardiovascular risk. We found evidence of population sub-structure and excess inter-marker
linkage disequilibrium, consistent with recent admixture. The estimated group admixture proportions were 78.1% African and
22.9% European, but differed according to geographic region. In multiple regression models, African ancestry was significantly
associated with decreased total cholesterol, decreased LDL-cholesterol, and decreased triglycerides, and also with increased
risk of insulin resistance. These observed associations between African ancestry and several lipid traits are consistent with
the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There
was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification.
These results demonstrate the potential for confounding of genetic associations with some cardiovascular disease-related traits
in large studies involving US African-Americans. |
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