许多影响血浆高密度脂蛋白胆固醇的常见遗传变异,低密度脂蛋白胆固醇(LDL-C),和甘油三酯分布已通过全基因组关联研究(GWAS)确定。然而,这些关联是否与年龄相关,在很大程度上被忽视了。我们在22,000多名欧裔美国人中进行了一项关联研究和荟萃分析,其中包括49种先前鉴定的GWAS变体和三种脂质性状,按年龄分层(男性:<50岁或≥50岁;女性:绝经前或绝经后)。对于每个变体,在两个年龄层次之间进行异质性检验,并使用显著的Phet值作为年龄特异性遗传效应的证据.我们确定了女性中的七个关联和男性中的八个关联,这些关联显示出年龄的暗示性异质性(Phet<0.05)。男性rs174547(FADS1)和LDL-C之间的关联显示出年龄组之间异质性的最多证据(Phet=1.74E-03,I(2)=89.8),与老年男性(P=1.39E-06)显着相关,但与年轻男性(P=0.99)无关。然而,没有一个暗示性修饰效应在多重测试的调整中幸存下来,突出了尽管样本量很大,但识别适度SNP-性状关联的修饰符的挑战。
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.