Published online before print April 14, 2009, doi: 10.1161/CIRCGENETICS.108.829473
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Original Articles |
Association of Blood Lipids With Common DNA Sequence Variants at 19 Genetic Loci in the Multiethnic United States National Health and Nutrition Examination Survey III
From the Massachusetts General Hospital (M.E.K., S.E.K.), Boston, Mass; Centers for Disease Control (C.L.S.), Hyattsville, Md; and Broad Institute of MIT/Harvard (A.S., C.G., N.P.B.), Cambridge, Mass.
Correspondence to Sekar Kathiresan, MD, Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, CZPN 5.252, Boston, MA 02115. skathiresan{at}partners.org
Received October 16, 2008; accepted February 13, 2009.
Background— Using the genome-wide association approach in individuals of European ancestry, we and others recently identified single-nucleotide polymorphisms (SNPs) at 19 loci as associated with blood lipids; 8 of these loci were novel. Whether these same SNPs associate with lipids in a broader range of ethnicities is unknown.
Methods and Results— We genotyped index SNPs at 19 loci in the Third United States National Health and Nutrition Examination Survey (n=7159), a population-based probability sample of the United States comprised primarily of non-Hispanic blacks, Mexican Americans, and non-Hispanic whites. We constructed ethnic-specific residual blood lipid levels after adjusting for age and gender. Ethnic-specific linear regression was used to test the association of genotype with blood lipids. To summarize the statistical evidence across 3 racial groups, we conducted a fixed-effects variance-weighted meta-analysis. After exclusions, there were 1627 non-Hispanic blacks, 1659 Mexican Americans, and 2230 non-Hispanic whites. At 5 loci (1p13 near CELSR2/PSRC1/SORT1, HMGCR, CETP, LPL, and APOA5), the index SNP was associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides in all 3 ethnic groups. At the remaining loci, there was mixed evidence by ethnic group. In meta-analysis, we found that, at 14 of the 19 loci, SNPs exceeded a nominal P<0.05.
Conclusions— At 5 loci including the recently discovered region on 1p13 near CELSR2/PSRC1/SORT1, the same SNP discovered in whites associates with blood lipids in non-Hispanic blacks and Mexican Americans. For the remaining loci, fine mapping and resequencing will be required to definitively evaluate the relevance of each locus in individuals of African and Hispanic ancestries.
Key Words: lipids • genetics • epidemiology • risk factors
CLINICAL PERSPECTIVE
Article handled by Guest Editor Donna K. Arnett, PhD.