Journal Article

Admixture mapping of quantitative trait loci for blood lipids in African-Americans

Analabha Basu, Hua Tang, Cora E. Lewis, Kari North, J. David Curb, Thomas Quertermous, Thomas H. Mosley, Eric Boerwinkle, Xiaofeng Zhu and Neil J. Risch

in Human Molecular Genetics

Volume 18, issue 11, pages 2091-2098
Published in print June 2009 | ISSN: 0964-6906
Published online March 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp122
Admixture mapping of quantitative trait loci for blood lipids in African-Americans

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Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), are highly heritable traits and major risk factors for atherosclerotic cardiovascular disease (CVD). Using individual ancestry estimates at marker locations across the genome, we present a novel quantitative admixture mapping analysis of all three lipid traits in a large sample of African-Americans from the Family Blood Pressure Program. Regression analysis was performed with both total and marker-location-specific European ancestry as explanatory variables, along with demographic covariates. Robust permutation analysis was used to assess statistical significance. Overall European ancestry was significantly correlated with HDL-C (negatively) and TG (positively), but not with LDL-C. We found strong evidence for a novel locus underlying HDL-C on chromosome 8q, which correlated negatively with European ancestry (P = .0014); the same location also showed positive correlation of European ancestry with TG levels. A region on chromosome 14q also showed significant negative correlation between HDL-C levels and European ancestry. On chromosome 15q, a suggestive negative correlation of European ancestry with TG and positive correlation with HDL-C was observed. Results with LDL-C were less significant overall. We also found significant evidence for genome-wide ancestry effects underlying the joint distribution of HDL-C and TG, not fully explained by the locus on chromosome 8. Our results are consistent with a genetic contribution to and may explain the healthier HDL-C and TG profiles found in Blacks versus Whites. The identified regions provide locations for follow-up studies of genetic variants underlying lipid variation in African-Americans and possibly other populations.

Journal Article.  5252 words.  Illustrated.

Subjects: Genetics and Genomics

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