Human Molecular Genetics Advance Access originally published online on March 20, 2009
Human Molecular Genetics 2009 18(11):2091-2098; doi:10.1093/hmg/ddp122
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Admixture mapping of quantitative trait loci for blood lipids in African-Americans
1 Institute for Human Genetics 2 Department of Epidemiology and Biostatistics, University of California San Francisco, 513 Parnassus Avenue, Room 901F HSW, San Francisco, CA 94143, USA 3 Department of Genetics 4 Department of Medicine, Stanford University, Palo Alto, CA, USA 5 Department of Medicine, University of Alabama, Birmingham, UK 6 Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA 7 Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA 8 University of Mississippi Medical Center, Jackson, MS, USA 9 School of Public Health, University of Texas Health Science Center, Houston, TX, USA 10 Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA 11 Kaiser Permanente Division of Research, Oakland, CA, USA
* To whom correspondence should be addressed. Tel: +1 4154761129; Fax: +1 4154762956; Email: basu{at}humgen.ucsf.edu (A.B.) and rischn{at}humgen.ucsf.edujp (N.J.R.)
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 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.