Admixture mapping of quantitative trait loci for blood lipids in African-Americans.
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.
Basu
Analabha
A
Institute for Human Genetics, University of California San Francisco, 513 Parnassus Avenue, Room 901F HSW, San Francisco, CA 94143, USA. basu@humgen.ucsf.edu
Tang
Hua
H
Lewis
Cora E
CE
North
Kari
K
Curb
J David
JD
Quertermous
Thomas
T
Mosley
Thomas H
TH
Boerwinkle
Eric
E
Zhu
Xiaofeng
X
Risch
Neil J
NJ
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood*; D044465:White People / Q000235:genetics
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides