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

التفاصيل البيبلوغرافية
العنوان: DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.
المؤلفون: 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.
المصدر: Genome Biol. 17:255 (2016)
بيانات النشر: Biomed Central Ltd
سنة النشر: 2016
المجموعة: PuSH - Publikationsserver des Helmholtz Zentrums München
مصطلحات موضوعية: Body Mass Index, C-reactive Protein, Coronary Heart Disease, Diabetes, Dna Methylation, Epigenome-wide Association Study, Inflammation
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
وصف الملف: application/pdf
اللغة: English
تدمد: 1474-7596
1474-760X
1465-6906
العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000390199000001; info:eu-repo/semantics/altIdentifier/isbn/1474-7596; info:eu-repo/semantics/altIdentifier/pissn/1474-760X; info:eu-repo/semantic; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=50168Test; urn:isbn:1474-7596; urn:issn:1474-760X; urn:issn:1465-6906
DOI: 10.1186/s13059-016-1119-5
الإتاحة: https://doi.org/10.1186/s13059-016-1119-5Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=50168Test
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.6A0EFCC0
قاعدة البيانات: BASE
الوصف
تدمد:14747596
1474760X
14656906
DOI:10.1186/s13059-016-1119-5