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

Jun Liu (), Elena Carnero-Montoro, Jenny 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. 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 Dijk, Najaf Amin, André G. Uitterlinden, Eric J. G. Sijbrands, Oscar H. Franco, Abbas Dehghan, Tim D. Spector, Josée Dupuis, Marie-France Hivert, Jerome I. Rotter, James B. Meigs, James S. Pankow, Joyce B. J. Meurs, Aaron Isaacs, Dorret I. Boomsma, Jordana T. Bell, Ayşe Demirkan () and Cornelia M. Duijn ()
Additional contact information
Jun Liu: Erasmus University Medical Center
Elena Carnero-Montoro: Erasmus University Medical Center
Jenny Dongen: Amsterdam UMC, Vrije Universiteit Amsterdam
Samantha Lent: Boston University School of Public Health
Ivana Nedeljkovic: Erasmus University Medical Center
Symen Ligthart: Erasmus University Medical Center
Pei-Chien Tsai: King’s College London
Tiphaine C. Martin: King’s College London
Pooja R. Mandaviya: Erasmus University Medical Center
Rick Jansen: Amsterdam UMC, Vrije Universiteit Amsterdam
Marjolein J. Peters: Erasmus University Medical Center
Liesbeth Duijts: Erasmus University Medical Center
Vincent W. V. Jaddoe: Erasmus University Medical Center
Henning Tiemeier: Erasmus University Medical Center
Janine F. Felix: Erasmus University Medical Center
Gonneke Willemsen: Amsterdam UMC, Vrije Universiteit Amsterdam
Eco J. C. Geus: Amsterdam UMC, Vrije Universiteit Amsterdam
Audrey Y. Chu: The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
Daniel Levy: The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
Shih-Jen Hwang: The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
Jan Bressler: University of Texas Health Science Center at Houston
Rahul Gondalia: University of North Carolina
Elias L. Salfati: Stanford University School of Medicine
Christian Herder: German Center for Diabetes Research (DZD)
Bertha A. Hidalgo: University of Alabama at Birmingham
Toshiko Tanaka: Translational Gerontology Branch, National Institute on Aging
Ann Zenobia Moore: Translational Gerontology Branch, National Institute on Aging
Rozenn N. Lemaitre: Cardiovascular Health Research Unit, Department of Medicine, University of Washington
Min A Jhun: School of Public Health, University of Michigan
Jennifer A. Smith: School of Public Health, University of Michigan
Nona Sotoodehnia: Cardiovascular Health Research Unit, Department of Medicine, University of Washington
Stefania Bandinelli: Azienda Sanitaria di Firenze
Luigi Ferrucci: Translational Gerontology Branch, National Institute on Aging
Donna K. Arnett: University of Kentucky
Harald Grallert: German Center for Diabetes Research (DZD)
Themistocles L. Assimes: Stanford University School of Medicine
Lifang Hou: Northwestern University Chicago
Andrea Baccarelli: Mailman School of Public Health, Columbia University
Eric A. Whitsel: University of North Carolina
Ko Willems Dijk: Leiden University Medical Center
Najaf Amin: Erasmus University Medical Center
André G. Uitterlinden: Erasmus University Medical Center
Eric J. G. Sijbrands: Erasmus University Medical Center
Oscar H. Franco: Erasmus University Medical Center
Abbas Dehghan: Erasmus University Medical Center
Tim D. Spector: King’s College London
Josée Dupuis: Boston University School of Public Health
Marie-France Hivert: Université de Sherbrooke
Jerome I. Rotter: The Institute for Translational Genomics and Population Sciences and Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
James B. Meigs: Harvard Medical School
James S. Pankow: University of Minnesota
Joyce B. J. Meurs: Maastricht University
Aaron Isaacs: Erasmus University Medical Center
Dorret I. Boomsma: Amsterdam UMC, Vrije Universiteit Amsterdam
Jordana T. Bell: King’s College London
Ayşe Demirkan: Erasmus University Medical Center
Cornelia M. Duijn: Erasmus University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10487-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10487-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10487-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().