Human Molecular Genetics Advance Access published online on March 20, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp122
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Admixture Mapping of Quantitative Trait Loci for Blood Lipids in African-Americans
1 Institute for Human Genetics, University of California, San Francisco 2 Department of Genetics, Stanford University 3 Department of Medicine, University of Alabama, Birmingham 4 Department of Epidemiology, University of North Carolina, Chapel Hill 5 Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu 6 Department of Medicine, Stanford University 7 University of Mississippi Medical Center, Jackson 8 School of Public Health, University of Texas Health Science Center, Houston 9 Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland 10 Department of Epidemiology and Biostatistics, UCSF 11 Kaiser Permanente Division of Research, Oakland
* Correspondence: Neil Risch, Ph.D., Institute for Human Genetics, University of California, San Francisco, 513 Parnassus Ave., Room 901F HSW, San Francisco, CA 94143, Tel: 415-476-1129, Fax: 415-476-2956, Email: RischN{at}humgen.ucsf.edu, BasuA{at}humgen.ucsf.edu
Received December 8, 2008; Revised January 29, 2009; Accepted March 12, 2009
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 (IA) estimates at marker locations across the genome, we present a novel Quantitative Admixture Mapping(QAM) analysis of all three lipid traits in a large sample of African Americans from the Family Blood Pressure Program(FBPP). 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.