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Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.

Thursday,2025-04-10 11:11 America/Los_Angeles — ecterry
TitleMethylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.
Publication TypeJournal Article
Year of Publication2025
AuthorsHu, Y, Haessler, J, Lundin, JI, Darst, BF, Whitsel, EA, Grove, M, Guan, W, Xia, R, Szeto, M, Raffield, LM, Ratliff, S, Wang, Y, Wang, X, Fohner, AE, Lynch, MT, Patel, YM, S Park, L, Xu, H, Mitchell, BD, Bis, JC, Sotoodehnia, N, Brody, JA, Psaty, BM, Peloso, GM, Tsai, MY, Rich, SS, Rotter, JI, Smith, JA, Kardia, SLR, Reiner, AP, Lange, L, Fornage, M, Pankow, JS, Graff, M, North, KE, Kooperberg, C, Peters, U
JournalClin Epigenetics
Volume17
Issue1
Pagination54
Date Published2025 Apr 02
ISSN1868-7083
KeywordsAdult, Aged, Alcohol Drinking, CpG Islands, DNA Methylation, Ethnicity, Female, Genome-Wide Association Study, Humans, Lipids, Male, Middle Aged, Racial Groups, Smoking, White People
Abstract<p>Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG levels, and also tested interactions between smoking or alcohol intake and methylation in their association with lipid levels. We identified novel CpG sites at 16 loci (P < 1.18E-7) with successful replication on 3,215 participants. One additional novel locus was identified in the self-reported White participants (P = 4.66E-8). Although no additional CpG sites were identified in the genome-wide interaction analysis, 13 reported CpG sites showed significant heterogeneous association across smoking or alcohol intake strata. By mapping novel and reported CpG sites to genes, we identified enriched pathways directly linked to lipid metabolism as well as ones spanning various biological functions. These findings provide new insights into the regulation of lipid concentrations.</p>
DOI10.1186/s13148-025-01859-3
Alternate JournalClin Epigenetics
PubMed ID40176173
PubMed Central IDPMC11967142
Grant ListN01HC95160 / HL / NHLBI NIH HHS / United States
75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005, and S10OD028685 / NH / NIH HHS / United States
75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1TR001881, DK063491, HL148610, and R01HL105756 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201800010I / HB / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
75N92020D00002 / HL / NHLBI NIH HHS / United States
75N92021D00002 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
U01HG007397 / HG / NHGRI NIH HHS / United States
HHSN268201800012C / HL / NHLBI NIH HHS / United States
75N92020D00005 / HL / NHLBI NIH HHS / United States
75N92021D00005 / WH / WHI NIH HHS / United States
U01HL054457, RC1HL100185, R01HL087660, R01HL119443, R01HL133221 / HL / NHLBI NIH HHS / United States
75N92022D00001 / NH / NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
DK063491 / / National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center /
HHSN268201800014I / HB / NHLBI NIH HHS / United States
U01CA164973 / CA / NCI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
S10 OD028685 / OD / NIH HHS / United States
75N92020D00001 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
HHSN268201800014C / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
75N92020D00003 / HL / NHLBI NIH HHS / United States
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
K08 HL116640 / HL / NHLBI NIH HHS / United States
75N92021D00001 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC1 HL100185 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
HHSN268201800013I / MD / NIMHD NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
HHSN268201800012I / HL / NHLBI NIH HHS / United States
75N92021D00003 / WH / WHI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
75N92020D00004 / HL / NHLBI NIH HHS / United States
HHSN268201800011C / HL / NHLBI NIH HHS / United States
75N92020D00007 / HL / NHLBI NIH HHS / United States
R01AG023629 / AG / NIA NIH HHS / United States
HHSN268201800013I, HHSN268201800014I, HHSN268201800015I, HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I / MD / NIMHD NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
R01HL105756, HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01AG023629, 75N92021D00006, U01HL080295, U01HL130114, K08HL116640, R01HL087652, R01HL092111, R01HL103612, R01HL111089, R01HL116747 and R01HL120393 / HL / NHLBI NIH HHS / United States
R01 HL133221 / HL / NHLBI NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
R01HG010297 / HG / NHGRI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201800015I / HB / NHLBI NIH HHS / United States
75N92020D00006 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
HHSN268201800011I / HB / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 HG010297 / HG / NHGRI NIH HHS / United States
U01 CA164973 / CA / NCI NIH HHS / United States
75N92021D00004 / 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
ePub date: 
25/04

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