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DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.

TitleDNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.
Publication TypeJournal Article
Year of Publication2016
AuthorsLigthart S, Marzi C, Aslibekyan S, Mendelson MM, Conneely KN, Tanaka T, Colicino E, Waite LL, Joehanes R, Guan W, Brody JA, Elks C, Marioni R, Jhun MA, Agha G, Bressler J, Ward-Caviness CK, Chen BH, Huan T, Bakulski K, Salfati EL, Fiorito G, Wahl S, Schramm K, Sha J, Hernandez DG, Just AC, Smith JA, Sotoodehnia N, Pilling LC, Pankow JS, Tsao PS, Liu C, Zhao W, Guarrera S, Michopoulos VJ, Smith AK, Peters MJ, Melzer D, Vokonas P, Fornage M, Prokisch H, Bis JC, Chu AY, Herder C, Grallert H, Yao C, Shah S, McRae AF, Lin H, Horvath S, Fallin D, Hofman A, Wareham NJ, Wiggins KL, Feinberg AP, Starr JM, Visscher PM, Murabito JM, Kardia SLR, Absher DM, Binder EB, Singleton AB, Bandinelli S, Peters A, Waldenberger M, Matullo G, Schwartz JD, Demerath EW, Uitterlinden AG, van Meurs JBJ, Franco OH, Chen Y-D I, Levy D, Turner ST, Deary IJ, Ressler KJ, Dupuis J, Ferrucci L, Ong KK, Assimes TL, Boerwinkle E, Koenig W, Arnett DK, Baccarelli AA, Benjamin EJ
Secondary AuthorsDehghan A
Corporate AuthorsWHI-EMPC Investigators, CHARGE epigenetics of Coronary Heart Disease
JournalGenome Biol
Volume17
Issue1
Pagination255
Date Published2016 12 12
ISSN1474-760X
KeywordsAfrican Americans, C-Reactive Protein, CpG Islands, DNA Methylation, Epigenesis, Genetic, European Continental Ancestry Group, Female, Gene Expression, Genetic Variation, Genome-Wide Association Study, Humans, Inflammation, Male, Nucleotide Motifs, Quantitative Trait Loci
Abstract

BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P 

CONCLUSION: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.
DOI10.1186/s13059-016-1119-5
Alternate JournalGenome Biol
PubMed ID27955697
PubMed Central IDPMC5151130
Grant ListR01 HL104135 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
G0401527 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
R01 HL133221 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100012C / HL / NHLBI NIH HHS / United States
P50 HL120163 / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R56 MH071537 / MH / NIMH NIH HHS / United States
R01 ES015172 / ES / NIEHS NIH HHS / United States
R01 MH071537 / MH / NIMH NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 ES021733 / ES / NIEHS NIH HHS / United States
C864/A8257 / CRUK_ / Cancer Research UK / United Kingdom
M01 RR000039 / RR / NCRR NIH HHS / United States
R01 MH096764 / MH / NIMH NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
/ RA / ARRA NIH HHS / United States
R01 HL076784 / HL / NHLBI NIH HHS / United States
G9502233 / MRC_ / Medical Research Council / United Kingdom
MC_EX_MR/L100002/1 / MRC_ / Medical Research Council / United Kingdom
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
MR/M023095/1 / MRC_ / Medical Research Council / United Kingdom
R01 AG042187 / AG / NIA NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
T32 HL098049 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC1 HL100185 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
P30 ES023515 / ES / NIEHS NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
MR/L00002/1 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
N01HC85080 / HL / NHLBI NIH HHS / United States
R00 ES023450 / ES / NIEHS 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