TY - JOUR T1 - Post-genome-wide association study challenges for lipid traits: describing age as a modifier of gene-lipid associations in the Population Architecture using Genomics and Epidemiology (PAGE) study. JF - Ann Hum Genet Y1 - 2013 A1 - Dumitrescu, Logan A1 - Carty, Cara L A1 - Franceschini, Nora A1 - Hindorff, Lucia A A1 - Cole, Shelley A A1 - Bůzková, Petra A1 - Schumacher, Fredrick R A1 - Eaton, Charles B A1 - Goodloe, Robert J A1 - Duggan, David J A1 - Haessler, Jeff A1 - Cochran, Barbara A1 - Henderson, Brian E A1 - Cheng, Iona A1 - Johnson, Karen C A1 - Carlson, Chris S A1 - Love, Shelly-Ann A1 - Brown-Gentry, Kristin A1 - Nato, Alejandro Q A1 - Quibrera, Miguel A1 - Anderson, Garnet A1 - Shohet, Ralph V A1 - Ambite, Jose Luis A1 - Wilkens, Lynne R A1 - Marchand, Loic Le A1 - Haiman, Christopher A A1 - Buyske, Steven A1 - Kooperberg, Charles A1 - North, Kari E A1 - Fornage, Myriam A1 - Crawford, Dana C KW - Adult KW - Aged KW - European Continental Ancestry Group KW - Female KW - Genetic Association Studies KW - Genome-Wide Association Study KW - Humans KW - Lipids KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci KW - Quantitative Trait, Heritable KW - Risk Factors AB -

Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age-dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or ≥50 years of age; females: pre- or postmenopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age-specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet < 0.05). The association between rs174547 (FADS1) and LDL-C in males displayed the most evidence for heterogeneity between age groups (Phet = 1.74E-03, I(2) = 89.8), with a significant association in older males (P = 1.39E-06) but not younger males (P = 0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP-trait associations despite large sample sizes.

VL - 77 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23808484?dopt=Abstract ER -