A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

We examined the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identified 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observed a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a low overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust a...

我们在一个包含16265名受试者的多族裔样本中，研究了循环白细胞中的DNA甲基化与血脂之间的关联。我们分别在欧洲人、非裔美国人和西班牙裔人群中鉴定出148个、35个和4个新关联，并通过跨族裔荟萃分析额外发现了186个新关联。我们观察到不同种族/族裔群体间效应方向高度一致，高密度脂蛋白与甘油三酯的效应量高度相关，与其他心脏代谢性状（cardio-metabolic traits）的表观基因组关联研究（epigenome-wide association studies）的关联重叠程度适中，且与迄今为止通过全基因组关联研究（genome-wide association studies）鉴定的脂质位点（lipid loci）重叠程度较低。30个CpG位点（CpGs）在至少2个种族/族裔群体中达到显著水平，其中7个与注释基因的表达相关。循环白细胞的DNA甲基化水平表现出robust a...