Jhun M, Mendelson M, Wilson R, Gondalia R, Joehanes R, Salfati E, Zhao X, Braun KVE, Do AN, Hedman ÅK, Zhang T, Carnero-Montoro E, Shen J, Bartz TM, Brody JA, Montasser ME, O'Connell JR, Yao C, Xia R, Boerwinkle E, Grove M, Guan W, Liliane P, Singmann P, Müller-Nurasyid M, Meitinger T, Gieger C, Peters A, Zhao W, Ware EB, Smith JA, Dhana K, van Meurs J, Uitterlinden A, Ikram MA, Ghanbari M, Zhi D, Gustafsson S, Lind L, Li S, Sun D, Spector TD, Chen YI, Damcott C, Shuldiner AR, Absher DM, Horvath S, Tsao PS, Kardia S, Psaty BM, Sotoodehnia N, Bell JT, Ingelsson E, Chen W, Dehghan A, Arnett DK, Waldenberger M, Hou L, Whitsel EA, Baccarelli A, Levy D, Fornage M, Irvin MR, Assimes TL
Nat Commun 12 (1) 3987 [2021-06-28; online 2021-06-28]
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.