|Title||Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Taylor 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 Authors||Fornage M|
|Corporate Authors||PAGE Study|
|Date Published||2013 May 01|
|Keywords||Female, Genetic Heterogeneity, Genome, Human, Genome-Wide Association Study, Humans, Lipids, Male, Polymorphism, Single Nucleotide, Population Groups|
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.
|Alternate Journal||BMC Genet|
|PubMed Central ID||PMC3669109|
|Grant List||P30 CA071789 / CA / NCI NIH HHS / United States |
U01 HG004790 / HG / NHGRI NIH HHS / United States