Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.

CpG Islands / genetics DNA Methylation / genetics Diabetes Mellitus, Type 2 / epidemiology Epigenesis, Genetic / genetics Epigenome Genome-Wide Association Study Humans Prospective Studies
Biomarkers DNA methylation Epigenetics Epigenome-wide association studies Meta-analysis Prediction Prospective studies Type 2 diabetes

Journal

Diabetologia
ISSN: 1432-0428
Titre abrégé: Diabetologia
Pays: Germany
ID NLM: 0006777

Informations de publication

Date de publication:
05 2022
Historique:
received: 14 12 2020
accepted: 15 11 2021
pubmed: 17 2 2022
medline: 12 4 2022
entrez: 16 2 2022
Statut: ppublish

Résumé

Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts. We conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK). The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values <1.1 × 10 By combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.

Identifiants

DOI: 10.1007/s00125-022-05652-2 PMID: 35169870 PMC: PMC8960572
pubmed: 35169870
doi: 10.1007/s00125-022-05652-2
pii: 10.1007/s00125-022-05652-2
pmc: PMC8960572
doi:

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

763-776

Subventions

Organisme : Medical Research Council
ID : MC_UU_12015/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Department of Health
ID : 16/136/68
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C864/A8257
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9502233
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L00002/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S019669/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Eliza Fraszczyk (E)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Annemieke M W Spijkerman (AMW)

Centre for Nutrition, Prevention and Health services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Yan Zhang (Y)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.

Stefan Brandmaier (S)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Felix R Day (FR)

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Li Zhou (L)

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

Paul Wackers (P)

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Martijn E T Dollé (MET)

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Vincent W Bloks (VW)

Department of Pediatrics, Section of Molecular Metabolism and Nutrition, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Xīn Gào (X)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.

Christian Gieger (C)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Jaspal Kooner (J)

Department of Cardiology, Ealing Hospital, Ealing, UK.
Imperial College Healthcare NHS Trust, London, UK.
MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
National Heart and Lung Institute, Imperial College London, London, UK.

Jennifer Kriebel (J)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

H Susan J Picavet (HSJ)

Centre for Nutrition, Prevention and Health services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Wolfgang Rathmann (W)

German Center for Diabetes Research (DZD), Neuherberg, Germany.
Institute for Biometrics and Epidemiology, German Diabetes Center, Auf'm Hennekamp, Duesseldorf, Germany.

Ben Schöttker (B)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Network Aging Research, University of Heidelberg, Heidelberg, Germany.

Marie Loh (M)

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

W M Monique Verschuren (WMM)

Centre for Nutrition, Prevention and Health services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Jana V van Vliet-Ostaptchouk (JV)

Genomics Coordination Center, Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Nicholas J Wareham (NJ)

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.

John C Chambers (JC)

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Department of Epidemiology and Biostatistics, Imperial College London, London, UK.

Ken K Ong (KK)

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Department of Paediatrics, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Harald Grallert (H)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Network Aging Research, University of Heidelberg, Heidelberg, Germany.

Mirjam Luijten (M)

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. mirjam.luijten@rivm.nl.

Harold Snieder (H)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. h.snieder@umcg.nl.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › Epigenome-wide association study of incident...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Epigenome-wide association study of incident...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Epigenome-wide association study of incident...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Epigenome-wide association study of incident...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › Epigenome-wide association study of incident...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Epigenome-wide association study of incident...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Epigenome-wide association study of incident...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Epigenome-wide association study of incident...