Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
复制标题
东亚个体的关联分析和欧洲个体的跨血统分析揭示了与胆固醇和甘油三酯水平相关的新位点
DOI：
10.1093/hmg/ddx062
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发表时间：
2017-05-01
影响因子：
3.5
通讯作者：
Sim, Xueling
中科院分区：
文献类型：
--
作者：
Spracklen, Cassandra N.;Chen, Peng;Sim, Xueling
全基因组关联研究（GWAS）的大规模荟萃分析已经确定了> 175个与空腹胆固醇水平相关的位点，包括总胆固醇（TC），高密度脂蛋白胆固醇（HDL-C），低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG）。由于祖先群体之间连锁不平衡（LD）结构和等位基因频率的差异，在额外的大样本中的研究可能会发现新的关联。我们对来自日本、菲律宾、韩国、中国、新加坡和台湾的24项研究的69,414名东亚个体进行了分期GWAS荟萃分析。这些荟萃分析发现，（P < 5 x 10（-8））三个新的与HDL-C相关的位点位于CD 163-APOBEC 1（P = 7.4 x 10（-9））、NCOA 2（P = 1.6 x 10（-8））和NID 2-PTGDR（P = 4.2 x 10（-8））附近，一个新的与TG相关的位点位于WDR 11-FGFR 2（P = 2.7 x 10（-10））附近。条件分析在CD 163-APOBEC 1附近发现了第二个信号。然后，我们将东亚荟萃分析的结果与来自全球脂质遗传学联盟的多达187，365名欧洲个体的关联结果进行了跨祖先荟萃分析。该分析鉴定了（log（10）贝叶斯因子α 6.1）8个额外的新脂质基因座。在所鉴定的12个基因座中，8个基因座的指数变异在先前的研究中与其他代谢性状至少表现出名义上的显著性，并且2个基因座在皮下脂肪组织中表现出BPTF和PDGFC的一致eQTL（P < 1 × 10（-5））。总之，这些分析确定了多个新的脂质位点，提供了新的潜在治疗靶点。
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified > 175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 x 10(-8)) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 x 10(-9)), NCOA2 (P = 1.6 x 10(-8)), and NID2-PTGDR (P = 4.2 x 10(-8)), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 x 10(-10)). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log(10)Bayes Factor a 6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 x 10(-5)) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.