دورية أكاديمية
DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
| العنوان: | DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases |
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| المؤلفون: | 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, 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 |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2016 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, Inflammation, DNA methylation, Epigenome-wide association study, C-reactive protein, Body mass index, Diabetes, Coronary heart disease, WIDE ASSOCIATION, ATHEROSCLEROSIS, African Americans, CpG Islands, Epigenesis, Genetic, European Continental Ancestry Group, Female, Gene Expression, Genetic Variation, Genome-Wide Association Study, Humans, Male, Nucleotide Motifs, Quantitative Trait Loci, WHI-EMPC Investigators, CHARGE epigenetics of Coronary Heart Disease |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1474-7596 |
| العلاقة: | Genome Biology; http://hdl.handle.net/10044/1/52885Test; https://dx.doi.org/10.1186/s13059-016-1119-5Test |
| DOI: | 10.1186/s13059-016-1119-5 |
| الإتاحة: | https://doi.org/10.1186/s13059-016-1119-5Test http://hdl.handle.net/10044/1/52885Test |
| حقوق: | © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0Test/), 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/1.0Test/) applies to the data made available in this article, unless otherwise stated. |
| رقم الانضمام: | edsbas.CDD92EB2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14747596 |
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| DOI: | 10.1186/s13059-016-1119-5 |