Published Online
on April 14, 2009

A more recent version of this article appeared on June 1, 2009

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Original Article

Association of Blood Lipids with Common DNA Sequence Variants at Nineteen Genetic Loci in the Multiethnic United States National Health and Nutrition Examination Survey III

Mary E. Keebler¹; Christopher L. Sanders²; Aarti Surti³; Candace Guiducci³; Noel P. Burtt³ and Sekar Kathiresan^1,4

¹ Massachusetts General Hospital, Boston, MA;
² Centers for Disease Control, Atlanta, GA;
³ Broad Institute of MIT and Harvard, Cambridge, MA

⁴ E-mail: skathiresan{at}partners.org

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; eight 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 U.S. 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 three 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 five 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 three 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 five 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: epidemiology • genetics • lipids • risk factors