@article{discovery1532717,
           month = {December},
          volume = {17},
            note = {{\copyright} The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.},
            year = {2016},
           title = {DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases},
         journal = {Genome Biology},
            issn = {1474-760X},
          author = {Ligthart, S and Marzi, C and Aslibekyan, S and Mendelson, MM and Conneely, KN and Tanaka, T and Colicino, E and Waite, LL and Joehanes, R and Guan, W and Brody, JA and Elks, C and Marioni, R and Jhun, MA and Agha, G and Bressler, J and Ward-Caviness, CK and Chen, BH and Huan, T and Bakulski, K and Salfati, EL and Fiorito, G and Wahl, S and Schramm, K and Sha, J and Hernandez, DG and Just, AC and Smith, JA and Sotoodehnia, N and Pilling, LC and Pankow, JS and Tsao, PS and Liu, C and Zhao, W and Guarrera, S and Michopoulos, VJ and Smith, AK and Peters, MJ and Melzer, D and Vokonas, P and Fornage, M and Prokisch, H and Bis, JC and Chu, AY and Herder, C and Grallert, H and Yao, C and Shah, S and McRae, AF and Lin, H and Horvath, S and Fallin, D and Hofman, A and Wareham, NJ and Wiggins, KL and Feinberg, AP and Starr, JM and Visscher, PM and Murabito, JM and Kardia, SL and Absher, DM and Binder, EB and Singleton, AB and Bandinelli, S and Peters, A and Waldenberger, M and Matullo, G and Schwartz, JD and Demerath, EW and Uitterlinden, AG and van Meurs, JB and Franco, OH and Chen, YI and Levy, D and Turner, ST and Deary, IJ and Ressler, KJ and Dupuis, J and Ferrucci, L and Ong, KK and Assimes, TL and Boerwinkle, E and Koenig, W and Arnett, DK and Baccarelli, AA and Benjamin, EJ and Dehghan, A},
        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 {\ensuremath{<}} 1.15 {$\times$} 10(-7)) in the discovery panel of European ancestry and replicated (P {\ensuremath{<}} 2.29 {$\times$} 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 {\ensuremath{<}} 8.47 {$\times$} 10(-5)), ten (17\%) CpG sites were associated with a nearby genetic variant (P {\ensuremath{<}} 2.50 {$\times$} 10(-3)), and 51 (88\%) were also associated with at least one related cardiometabolic entity (P {\ensuremath{<}} 9.58 {$\times$} 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.},
             url = {http://dx.doi.org/10.1186/s13059-016-1119-5},
        keywords = {Body mass index, C-reactive protein, Coronary heart disease, DNA methylation, Diabetes, Epigenome-wide association study, Inflammation}
}