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Ligthart, S.* ; Marzi, C. ; Aslibekyan, S.* ; Mendelson, M.M.* ; Conneely, K.N.* ; Tanaka, T.* ; Colicino, E.* ; Waite, L.L.* ; Joehanes, R.* ; Guan, W.* ; Brody, J.A.* ; Elks, C.E.* ; Marioni, R.E.* ; Jhun, M.A.* ; Agha, G.* ; Bressler, J.* ; Ward-Caviness, C.K. ; Chen, B.H.* ; Huan, T.* ; Bakulski, K.* ; Salfati, E.L.* ; Fiorito, G.* ; Wahl, S. ; Schramm, K. ; Sha, J.* ; Hernandez, D.G.* ; Just, A.C.* ; Smith, J.A.* ; Sotoodehnia, N.* ; Pilling, L.C.* ; Pankow, J.S.* ; Tsao, P.S.* ; Liu, C.* ; Zhao, W.* ; Guarrera, S.* ; Michopoulos, V.J.* ; Smith, A.K.* ; Peters, M.J.* ; Melzer, D.* ; Vokonas, P.* ; Fornage, M.* ; Prokisch, H. ; Bis, J.C.* ; Chu, A.Y.* ; Herder, C.* ; Grallert, H. ; Yao, C.* ; Shah, S.* ; McRae, A.F.* ; Lin, H.* ; Horvath, S.* ; Fallin, D.* ; Hofman, A.* ; Wareham, N.J.* ; Wiggins, K.L.* ; Feinberg, A.P.* ; Starr, J.M.* ; Visscher, P.M.* ; Murabito, J.M.* ; Kardia, S.L.R.* ; Absher, D.M.* ; Binder, E.B.* ; Singleton, A.B.* ; Bandinelli, S.* ; Peters, A. ; Waldenberger, M. ; Matullo, G.* ; Schwartz, J.D.* ; Demerath, E.W.* ; Uitterlinden, A.G.* ; Meurs, J.B.J.* ; Franco, O.H.* ; Chen, Y.D.I.* ; Levy, D.* ; Turner, S.T.* ; Deary, I.J.*

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

Genome Biol. 17:255 (2016)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
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 < 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. 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Body Mass Index ; C-reactive Protein ; Coronary Heart Disease ; Diabetes ; Dna Methylation ; Epigenome-wide Association Study ; Inflammation; Wide Association; Atherosclerosis
ISSN (print) / ISBN 1474-760X
e-ISSN 1465-6906
Journal Genome Biology
Quellenangaben Volume: 17, Issue: 1, Pages: , Article Number: 255 Supplement: ,
Publisher BioMed Central
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)