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DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.
Tuesday,2017-05-02 15:25 America/Los_Angeles — ecterry
| Title | DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Ligthart, 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-DI, 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, Dehghan, A |
| Corporate/Institutional Authors | WHI-EMPC Investigators, CHARGE epigenetics of Coronary Heart Disease |
| Journal | Genome Biol |
| Volume | 17 |
| Issue | 1 |
| Pagination | 255 |
| Date Published | 2016 Dec 12 |
| ISSN | 1474-760X |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>RESULTS: </b>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 < 1.15 × 10(-7)) in the discovery panel of European ancestry and replicated (P < 2.29 × 10(-4)) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10(-5)), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10(-3)), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10(-5)). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.</p><p><b>CONCLUSION: </b>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.</p> |
| DOI | 10.1186/s13059-016-1119-5 |
| Alternate Journal | Genome Biol. |
| PubMed ID | 27955697 |
| PubMed Central ID | PMC5151130 |
| Grant List | 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 HL104135 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI 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 HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States M01 RR000039 / RR / NCRR NIH HHS / United States R01 MH096764 / MH / NIMH NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL076784 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL119443 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI 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 HHSN268201100005I / HL / NHLBI NIH HHS / United States U01 HL054457 / HL / NHLBI NIH HHS / United States HHSN268201500001I / HL / NHLBI NIH HHS / United States UL1 TR000454 / TR / NCATS NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States 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 HHSN268201100007I / 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 N01HC85080 / HL / NHLBI 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 N01HC85081 / HL / NHLBI NIH HHS / United States |
ePub date:
16/12