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Characterization of whole-genome autosomal differences of DNA methylation between men and women

Lookup NU author(s): Dr So-Youn Shin, Professor Caroline Relton

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: Disease risk and incidence between males and females reveal differences, and sex is an important component of any investigation of the determinants of phenotypes or disease etiology. Further striking differences between men and women are known, for instance, at the metabolic level. The extent to which men and women vary at the level of the epigenome, however, is not well documented. DNA methylation is the best known epigenetic mechanism to date.Results: In order to shed light on epigenetic differences, we compared autosomal DNA methylation levels between men and women in blood in a large prospective European cohort of 1799 subjects, and replicated our findings in three independent European cohorts. We identified and validated 1184 CpG sites to be differentially methylated between men and women and observed that these CpG sites were distributed across all autosomes. We showed that some of the differentially methylated loci also exhibit differential gene expression between men and women. Finally, we found that the differentially methylated loci are enriched among imprinted genes, and that their genomic location in the genome is concentrated in CpG island shores.Conclusion: Our epigenome-wide association study indicates that differences between men and women are so substantial that they should be considered in design and analyses of future studies.


Publication metadata

Author(s): Singmann P, Shem-Tov D, Wahl S, Grallert H, Fiorito G, Shin SY, Schramm K, Wolf P, Kunze S, Baran Y, Guarrera S, Vineis P, Krogh V, Panico S, Tumino R, Kretschmer A, Gieger C, Peters A, Prokisch H, Relton CL, Matullo G, Illig T, Waldenberger M, Halperin E

Publication type: Article

Publication status: Published

Journal: Epigenetics & Chromatin

Year: 2015

Volume: 8

Online publication date: 19/10/2015

Acceptance date: 29/09/2015

Date deposited: 21/07/2016

ISSN (print): 1756-8935

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/s13072-015-0035

DOI: 10.1186/s13072-015-0035


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Funding

Funder referenceFunder name
German Federal Ministry of Education and Research (BMBF)
MRC Integrative Epidemiology Unit
Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
Oak Foundation
Associazione Italiana per la Ricerca sul Cancro
Compagnia di San Paolo for the EPIC, EPICOR, and EPICOR2 projects
Edmond J. Safra Center for Bioinformatics at Tel-Aviv University
Federal Ministry of Health (Berlin, Germany)
Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany
Human Genetics Foundation (HuGeF)
Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia (Dusseldorf, Germany)
UK Medical Research Council
UK Medical Research Council Integrative Epidemiology Unit
1094-33.2/2010German-Israeli Foundation for Scientific Research and Development
1425/13Israel Science Foundation
2012304United States-Israel Binational Science Foundation
261433European Union
102215/2/13/2Wellcome Trust
310Helmholtz-Russia Joint Research Group (HRJRG)
603288European Union
279233European Union (EPIC-CVD 7th FP)
305280European Union
BB/I025751/1UK Biotechnology and Biological Sciences Research Council
BB/I025263/1UK Biotechnology and Biological Sciences Research Council
FP7-Health-F5-2012European Union
III-1217615National Science Foundation
MC_UU_12013_2University of Bristol

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