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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.
Liu, Jun; Carnero-Montoro, Elena; van Dongen, Jenny; Lent, Samantha; Nedeljkovic, Ivana; Ligthart, Symen; Tsai, Pei-Chien; Martin, Tiphaine C; Mandaviya, Pooja R; Jansen, Rick; Peters, Marjolein J; Duijts, Liesbeth; Jaddoe, Vincent W V; Tiemeier, Henning; Felix, Janine F; Willemsen, Gonneke; de Geus, Eco J C; Chu, Audrey Y; Levy, Daniel; Hwang, Shih-Jen; Bressler, Jan; Gondalia, Rahul; Salfati, Elias L; Herder, Christian; Hidalgo, Bertha A; Tanaka, Toshiko; Moore, Ann Zenobia; Lemaitre, Rozenn N; Jhun, Min A; Smith, Jennifer A; Sotoodehnia, Nona; Bandinelli, Stefania; Ferrucci, Luigi; Arnett, Donna K; Grallert, Harald; Assimes, Themistocles L; Hou, Lifang; Baccarelli, Andrea; Whitsel, Eric A; van Dijk, Ko Willems; Amin, Najaf; Uitterlinden, André G; Sijbrands, Eric J G; Franco, Oscar H; Dehghan, Abbas; Spector, Tim D; Dupuis, Josée; Hivert, Marie-France; Rotter, Jerome I; Meigs, James B.
Afiliação
  • Liu J; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands. jun.liu@ndph.ox.ac.uk.
  • Carnero-Montoro E; Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7FL, UK. jun.liu@ndph.ox.ac.uk.
  • van Dongen J; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Lent S; Center for Genomics and Oncological Research, GENYO, Pfizer/University of Granada/Andalusian Government, PTS, Granada, 18007, Spain.
  • Nedeljkovic I; Department of Twin Research and Genetic Epidemiology, King's College London, London, WC2R 2LS, UK.
  • Ligthart S; Department of Biological Psychology, Amsterdam Public Health (APH) research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands.
  • Tsai PC; Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Martin TC; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Mandaviya PR; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Jansen R; Department of Twin Research and Genetic Epidemiology, King's College London, London, WC2R 2LS, UK.
  • Peters MJ; Department of Biomedical Sciences, Chang Gung University, Taoyuan, 333, Taiwan.
  • Duijts L; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, 333, Taiwan.
  • Jaddoe VWV; Department of Twin Research and Genetic Epidemiology, King's College London, London, WC2R 2LS, UK.
  • Tiemeier H; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Felix JF; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Willemsen G; Department of Internal Medicine, Section of Pharmacology Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • de Geus EJC; Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands.
  • Chu AY; Department of Internal Medicine, Section of Pharmacology Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Levy D; Division of Neonatology, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Hwang SJ; Division of Respiratory Medicine, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Bressler J; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Gondalia R; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Salfati EL; Generation R Study Group, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Herder C; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Hidalgo BA; Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, MA, 02115, USA.
  • Tanaka T; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Moore AZ; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Lemaitre RN; Generation R Study Group, Erasmus University Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Jhun MA; Department of Biological Psychology, Amsterdam Public Health (APH) research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands.
  • Smith JA; Department of Biological Psychology, Amsterdam Public Health (APH) research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, 1081BT, The Netherlands.
  • Sotoodehnia N; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20814, USA.
  • Bandinelli S; The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health, Framingham, MA, 01702, USA.
  • Ferrucci L; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20814, USA.
  • Arnett DK; The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health, Framingham, MA, 01702, USA.
  • Grallert H; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20814, USA.
  • Assimes TL; The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health, Framingham, MA, 01702, USA.
  • Hou L; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Baccarelli A; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Whitsel EA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • van Dijk KW; German Center for Diabetes Research (DZD), München-Neuherberg, 85764, Germany.
  • Amin N; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany.
  • Uitterlinden AG; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany.
  • Sijbrands EJG; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
  • Franco OH; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, 21224, USA.
  • Dehghan A; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, 21224, USA.
  • Spector TD; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
  • Dupuis J; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Hivert MF; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Rotter JI; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
  • Meigs JB; Geriatric Unit, Azienda Sanitaria di Firenze, Florence, 50137, Italy.
Nat Commun ; 10(1): 2581, 2019 06 13.
Article em En | MEDLINE | ID: mdl-31197173
ABSTRACT
Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metilação de DNA / Diabetes Mellitus Tipo 2 / Glucose / Insulina / Obesidade Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metilação de DNA / Diabetes Mellitus Tipo 2 / Glucose / Insulina / Obesidade Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Ano de publicação: 2019 Tipo de documento: Article