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Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study.
Monday,2015-03-09 16:26 America/Los_Angeles — zdrager
| 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, Bůzková, 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, Fornage, M |
| Corporate/Institutional Authors | PAGE Study, |
| Journal | BMC Genet |
| Volume | 14 |
| Pagination | 33 |
| Date Published | 2013 |
| ISSN | 1471-2156 |
| Keywords | Female, Genetic Heterogeneity, Genome, Human, Genome-Wide Association Study, Humans, Lipids, Male, Polymorphism, Single Nucleotide, Population Groups |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>RESULTS: </b>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 < 0.001. There was evidence for heterogeneity by sex for two SNPs for ln(TG) in the APOA1/C3/A4/A5/BUD13 gene cluster: rs28927680 (p(het) = 7.4 x 10(-7)) and rs3135506 (p(het) = 4.3 x 10(-4)one SNP in PLTP for HDL levels (rs7679; p(het) = 9.9 x 10(-4)), and one in HMGCR for LDL levels (rs12654264; p(het) = 3.1 x 10(-5)). We replicated heterogeneity by sex in five of seventeen loci previously reported by genome-wide studies (binomial p = 0.0009). We also present results for other racial/ethnic groups in the supplementary materials, to provide a resource for future meta-analyses.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1186/1471-2156-14-33 |
| Alternate Journal | BMC Genet. |
| PubMed ID | 23634756 |
| PubMed Central ID | PMC3669109 |
| Grant List | U01 HG004790 / HG / NHGRI NIH HHS / United States |