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一项多民族白细胞 DNA 甲基化与血脂的全基因组关联研究。

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

机构信息

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Nat Commun. 2021 Jun 28;12(1):3987. doi: 10.1038/s41467-021-23899-y.

Abstract

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 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 observe 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 largely non-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 and consistent association with blood lipid levels across multiple racial/ethnic groups.

摘要

我们在一个包含 16265 名受试者的多民族样本中,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中确定了 148、35 和 4 个新的关联,通过跨种族荟萃分析还确定了另外 186 个新的关联。我们观察到,在不同种族/民族群体中,效应的方向高度一致,高密度脂蛋白和甘油三酯的效应大小相关性很高,与其他心血管代谢特征的全基因组关联研究的关联有适度重叠,与迄今为止通过全基因组关联研究确定的脂质基因座基本没有重叠。至少有 2 个种族/民族群体中的 30 个 CpG 达到了显著水平,其中 7 个 CpG 与注释基因的表达有关。CPT1A 注释的 CpG 显示出受甘油三酯水平影响的证据。循环白细胞中的 DNA 甲基化水平与多个种族/民族群体的血脂水平之间存在稳健且一致的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec4/8238961/18dcedae56f1/41467_2021_23899_Fig1_HTML.jpg

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