Pulse lineResearch With Heart Logo

Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study.

TitleInvestigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study.
Publication TypeJournal Article
Year of Publication2013
AuthorsTaylor KC, Carty CL, Dumitrescu L, Bůžková P, Cole SA, Hindorff L, Schumacher FR, Wilkens LR, Shohet RV, P Quibrera M, Johnson KC, Henderson BE, Haessler J, Franceschini N, Eaton CB, Duggan DJ, Cochran B, Cheng I, Carlson CS, Brown-Gentry K, Anderson G, Ambite JLuis, Haiman C, Le Marchand L, Kooperberg C, Crawford DC, Buyske S, North KE
Secondary AuthorsFornage M
Corporate AuthorsPAGE Study
JournalBMC Genet
Volume14
Pagination33
Date Published2013 May 01
ISSN1471-2156
KeywordsFemale, Genetic Heterogeneity, Genome, Human, Genome-Wide Association Study, Humans, Lipids, Male, Polymorphism, Single Nucleotide, Population Groups
Abstract

BACKGROUND: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ~100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits exhibited heterogeneity by sex in the Population Architecture using Genomics and Epidemiology (PAGE) study.

RESULTS: A sex-stratified meta-analysis was performed for 49 GWAS-identified SNPs for fasting HDL-C, LDL-C, and ln(TG) levels among adults self-identified as European American (25,013). Heterogeneity by sex was established when phet

CONCLUSIONS: We provide further evidence for sex-specific effects of SNPs in the APOA1/C3/A4/A5/BUD13 gene cluster, PLTP, and HMGCR on fasting triglyceride levels in European Americans from the PAGE study. Our findings emphasize the need for considering context-specific effects when interpreting genetic associations emerging from GWAS, and also highlight the difficulties in replicating interaction effects across studies and across racial/ethnic groups.

DOI10.1186/1471-2156-14-33
Alternate JournalBMC Genet
PubMed ID23634756
PubMed Central IDPMC3669109
Grant ListP30 CA071789 / CA / NCI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States