An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Jun Liu; Elena Carnero-Montoro; Jenny van Dongen; Samantha Lent; Ivana Nedeljkovic; Symen Ligthart; Pei-Chien Tsai; Tiphaine C. Martin; Pooja R. Mandaviya; Rick Jansen; Marjolein J. Peters; Liesbeth Duijts; Vincent W. V. Jaddoe; Henning Tiemeier; Janine F. Felix; Gonneke Willemsen; Eco J. C. de Geus; Audrey Y. Chu; Daniel Levy; Shih-Jen Hwang; Jan Bressler; Rahul Gondalia; Elias L. Salfati; Christian Herder; Bertha A. Hidalgo; Toshiko Tanaka; Ann Zenobia Moore; Rozenn N. Lemaitre; Min A. Jhun; Jennifer A. Smith; Nona Sotoodehnia; Stefania Bandinelli; Luigi Ferrucci; Donna K. Arnett; Harald Grallert; Themistocles L. Assimes; Lifang Hou; Andrea Baccarelli; Eric A. Whitsel; Ko Willems van Dijk; Najaf Amin; Andre G. Uitterlinden; Eric J. G. Sijbrands; Oscar H. Franco; Abbas Dehghan; Tim D. Spector; Josee Dupuis; Marie-France Hivert; Jerome Rotter; James B. Meigs; James S. Pankow; Joyce B. J. van Meurs; Aaron Isaacs; Dorret Boomsma; Jordana T. Bell; Ayse Demirkan; Cornelia M. van Duijn

doi:10.1038/s41467-019-10487-4

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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Jun Liu, Elena Carnero-Montoro, Jenny van Dongen, Samantha Lent, Ivana Nedeljkovic, Symen Ligthart, Pei-Chien Tsai, Tiphaine C. Martin, Pooja R. Mandaviya, Rick Jansen, …

Nature communications, Vol.10(1), pp.2581-11

13/06/2019

DOI: https://doi.org/10.1038/s41467-019-10487-4

PMID: 31197173

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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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Title: An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis
Creators: Jun Liu - Erasmus MC
Elena Carnero-Montoro - College Station Medical Center
Jenny van Dongen - Vrije Universiteit Amsterdam
Samantha Lent - Boston University
Ivana Nedeljkovic - Erasmus MC
Symen Ligthart - Erasmus MC
Pei-Chien Tsai - King's College London
Tiphaine C. Martin - King's College London
Pooja R. Mandaviya - Erasmus MC
Rick Jansen - Amsterdam Neuroscience
Marjolein J. Peters - Erasmus MC
Liesbeth Duijts - Erasmus MC
Vincent W. V. Jaddoe - Erasmus MC
Henning Tiemeier - Erasmus MC
Janine F. Felix - Erasmus MC
Gonneke Willemsen - Vrije Universiteit Amsterdam
Eco J. C. de Geus - Vrije Universiteit Amsterdam
Audrey Y. Chu - National Heart Lung and Blood Institute
Daniel Levy - National Heart Lung and Blood Institute
Shih-Jen Hwang - NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20814 USA
Jan Bressler - The University of Texas Health Science Center at Houston
Rahul Gondalia - University of North Carolina at Chapel Hill
Elias L. Salfati - Stanford University
Christian Herder - German Center for Diabetes Research
Bertha A. Hidalgo - University of Alabama at Birmingham
Toshiko Tanaka - National Institute on Aging
Ann Zenobia Moore - National Institute on Aging
Rozenn N. Lemaitre - University of Washington
Min A. Jhun - University of Michigan–Ann Arbor
Jennifer A. Smith - University of Michigan–Ann Arbor
Nona Sotoodehnia - University of Washington
Stefania Bandinelli - Azienda Sanitaria di Firenze
Luigi Ferrucci - National Institute on Aging
Donna K. Arnett - University of Kentucky
Harald Grallert - German Center for Diabetes Research
Themistocles L. Assimes - Stanford University
Lifang Hou - Northwestern University
Andrea Baccarelli - Columbia University
Eric A. Whitsel - University of North Carolina at Chapel Hill
Ko Willems van Dijk - Leiden University Medical Center
Najaf Amin - Erasmus MC
Andre G. Uitterlinden - Erasmus MC
Eric J. G. Sijbrands - Erasmus MC
Oscar H. Franco - University of Bern
Abbas Dehghan - Imperial College London
Tim D. Spector - King's College London
Josee Dupuis - Boston University
Marie-France Hivert - College Station Medical Center
Jerome Rotter - Harbor–UCLA Medical Center
James B. Meigs - Harvard University
James S. Pankow - University of Minnesota
Joyce B. J. van Meurs - Maastricht University
Aaron Isaacs - Maastricht University
Dorret Boomsma - Vrije Universiteit Amsterdam
Jordana T. Bell - King's College London
Ayse Demirkan - University Medical Center Groningen
Cornelia M. van Duijn - Centre for Human Drug Research
Publication Details: Nature communications, Vol.10(1), pp.2581-11
Publisher: NATURE PORTFOLIO
Number of pages: 11
Date published: 13/06/2019
Grant note: VENI 91616165 / ZonMw; Netherlands Organization for Health Research and Development Personalized pREvention of Chronic DIseases consortium (PRECeDI) (H2020-MSCA-RISE-2014) 633595 / European Union's Horizon 2020 research and innovation programme CVON2012-03 / CardioVasculair Onderzoek Nederland of the Netherlands Heart Foundation ERC-2014-CoG-648916 / European Research Council; European Research Council (ERC); European Commission ZIAHL006001 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) VIDI 016.136.361 / Netherlands Organization for Health Research and Development BBSRC BB/S020845/1 / JPI ERA-HDHL DIMENSION project U01-AG061359 / NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) 667375 / Common mechanisms and pathways in Stroke and Alzheimer's disease (CoSTREAM) project
Identifiers: 99928759802346
Academic Unit: Institute for Sustainability; Surrey Institute for People-Centred AI; School of Biosciences
Language: English
Resource Type: Journal article

An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

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