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

Author:

Jhun Min-AORCID,Mendelson MichaelORCID,Wilson RoryORCID,Gondalia Rahul,Joehanes RobyORCID,Salfati Elias,Zhao Xiaoping,Braun Kim Valeska EmilieORCID,Do Anh Nguyet,Hedman Åsa K.ORCID,Zhang Tao,Carnero-Montoro ElenaORCID,Shen Jincheng,Bartz Traci M.,Brody Jennifer A.ORCID,Montasser May E.,O’Connell Jeff R.,Yao ChenORCID,Xia Rui,Boerwinkle Eric,Grove Megan,Guan Weihua,Liliane Pfeiffer,Singmann PaulaORCID,Müller-Nurasyid MartinaORCID,Meitinger Thomas,Gieger Christian,Peters AnnetteORCID,Zhao WeiORCID,Ware Erin B.ORCID,Smith Jennifer A.ORCID,Dhana Klodian,van Meurs Joyce,Uitterlinden AndreORCID,Ikram Mohammad ArfanORCID,Ghanbari MohsenORCID,Zhi Deugi,Gustafsson StefanORCID,Lind Lars,Li Shengxu,Sun Dianjianyi,Spector Tim D.ORCID,Chen Yii-der Ida,Damcott ColeenORCID,Shuldiner Alan R.,Absher Devin M.,Horvath SteveORCID,Tsao Philip S.ORCID,Kardia Sharon,Psaty Bruce M.,Sotoodehnia Nona,Bell Jordana T.ORCID,Ingelsson Erik,Chen WeiORCID,Dehghan Abbas,Arnett Donna K.ORCID,Waldenberger MelanieORCID,Hou Lifang,Whitsel Eric A.,Baccarelli Andrea,Levy Daniel,Fornage MyriamORCID,Irvin Marguerite R.,Assimes Themistocles L.ORCID

Abstract

AbstractHere 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.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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