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

TitleA multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.
Publication TypeJournal Article
Year of Publication2021
AuthorsJhun M-A, Mendelson M, Wilson R, Gondalia R, Joehanes R, Salfati E, Zhao X, Braun KValeska Em, Do ANguyet, 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 MArfan, Ghanbari M, Zhi D, Gustafsson S, Lind L, Li S, Sun D, Spector TD, Chen Y-D I, 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
JournalNat Commun
Volume12
Issue1
Pagination3987
Date Published2021 06 28
ISSN2041-1723
KeywordsAdult, African Americans, Aged, Carnitine O-Palmitoyltransferase, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenome, Epigenomics, European Continental Ancestry Group, Female, Hispanic Americans, Humans, Leukocytes, Lipids, Lipoproteins, HDL, Male, Middle Aged, Quantitative Trait Loci
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.

DOI10.1038/s41467-021-23899-y
Alternate JournalNat Commun
PubMed ID34183656
PubMed Central IDPMC8238961
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL104135 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
/ DH_ / Department of Health / United Kingdom
N01HC85086 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
R01 HL133221 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
R01 ES020836 / ES / NIEHS NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC1 HL100185 / HL / NHLBI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
HHSN268201100003I / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
HHSN268201300006C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
R21 MD013296 / MD / NIMHD NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
R01 HL092111 / HL / NHLBI NIH HHS / United States