DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
WHI-EMPC Investigators(Erasmus MC), Symen Ligthart(Erasmus MC), CHARGE epigenetics of Coronary Heart Disease(University of Alabama at Birmingham), Carola Marzi(Boston Children's Hospital), Stella Aslibekyan(Emory University), Michael Mendelson(Boston Children's Hospital), Karen N. Conneely(Harvard University), Toshiko Tanaka(National Institute on Aging), Elena Colicino(Harvard University), Lindsay L. Waite(University of Minnesota), Roby Joehanes(Harvard University), Weihua Guan(University of Minnesota), Jennifer A. Brody(The University of Queensland), Cathy E. Elks(University of Cambridge), Riccardo E. Marioni(Harvard University), Min A. Jhun(University of Michigan), Golareh Agha(Harvard University), Jan Bressler(National Institutes of Health), Cavin Ward‐Caviness(National Institutes of Health), Brian H. Chen(National Institutes of Health), Tianxiao Huan(National Institutes of Health), Kelly M. Bakulski(Johns Hopkins University), Elias Salfati(Helmholtz Zentrum München), Giovanni Fiorito(Helmholtz Zentrum München), Simone Wahl(Helmholtz Zentrum München), Katharina Schramm(Helmholtz Zentrum München), Jin Sha(Harvard University), Dena Hernández(University of Michigan), Allan C. Just(Harvard University), Jennifer A. Smith(University of Exeter), Nona Sotoodehnia(University of Minnesota), Luke C. Pilling(Palo Alto University), James S. Pankow(National Institutes of Health), Philip S. Tsao(Palo Alto University), Chunyu Liu(Boston University), Wei Zhao(Emory University), Simonetta Guarrera(Emory University), Vasiliki Michopoulos(Emory University), Alicia K. Smith(Emory University), Marjolein J. Peters(Boston University), David Melzer(University of Exeter), Pantel Vokonas(Boston University), Myriam Fornage(University of Washington), Holger Prokisch(National Institutes of Health), Joshua C. Bis(University of Washington), Audrey Y. Chu(National Institutes of Health), Christian Herder(National Institutes of Health), Harald Grallert(Translational Research Institute), Chen Yao(National Institutes of Health), Sonia Shah(Translational Research Institute), Allan F. McRae(Translational Research Institute), Honghuang Lin(Boston University), Steve Horvath(Harvard University), M. Daniele Fallin(Johns Hopkins University), Albert Hofman(Harvard University), Nicholas J. Wareham(Johns Hopkins University), Kerri L. Wiggins(University of Washington), Andrew P. Feinberg(Translational Research Institute), John M. Starr(Institute of Genetics and Cancer), Peter M. Visscher(Translational Research Institute), Joanne M. Murabito(HudsonAlpha Institute for Biotechnology), Sharon L. R. Kardia(Emory University), Devin Absher(National Institute on Aging), Elisabeth B. Binder(Emory University), Andrew B. Singleton(Helmholtz Zentrum München), Stefania Bandinelli(Helmholtz Zentrum München), Annette Peters(Helmholtz Zentrum München), Mélanie Waldenberger(Boston University), Giuseppe Matullo(University of Minnesota), Joel Schwartz(Harvard University), Ellen W. Demerath(University of Minnesota), André G. Uitterlinden(Erasmus MC), Joyce B. J. van Meurs(Erasmus MC), Oscar H. Franco(National Institutes of Health), Yii‐Der Ida Chen(Mayo Clinic), Daniel Levy(National Institutes of Health), Stephen T. Turner(Mayo Clinic), Ian J. Deary(Institute of Genetics and Cancer), Kerry J. Ressler(Harvard University), Josée Dupuis(Boston University), Luigi Ferrucci(National Institute on Aging), Ken K. Ong(University of Cambridge), Themistocles L. Assimes(Universität Ulm), Eric Boerwinkle(University of Kentucky), Wolfgang Köenig(Harvard University), Donna K. Arnett(Boston University), Andrea Baccarelli(Harvard University), Emelia J. Benjamin(Boston University), Abbas Dehghan(Erasmus MC)
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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: ). 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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