Journal
EPIGENETICS & CHROMATIN
Volume 8, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13072-015-0035-3
Keywords
DNA methylation; EWAS; Sex; Enrichment analysis; CpG; Imprinting; KORA; ALSPAC; EPICOR
Categories
Funding
- Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany
- German Federal Ministry of Education and Research (BMBF)
- Federal Ministry of Health (Berlin, Germany)
- Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia (Dusseldorf, Germany)
- Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
- European Union [261433, 603288, FP7-Health-F5-2012, 305280]
- Helmholtz-Russia Joint Research Group (HRJRG) [310]
- Israel Science Foundation [1425/13]
- United States-Israel Binational Science Foundation [2012304]
- German-Israeli Foundation for Scientific Research and Development [1094-33.2/2010]
- National Science Foundation [III-1217615]
- Edmond J. Safra Center for Bioinformatics at Tel-Aviv University
- UK Medical Research Council Integrative Epidemiology Unit
- University of Bristol [MC_UU_12013_2]
- UK Medical Research Council
- Wellcome Trust [102215/2/13/2]
- UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]
- MRC Integrative Epidemiology Unit
- Oak Foundation
- Compagnia di San Paolo for the EPIC, EPICOR, and EPICOR2 projects
- Human Genetics Foundation (HuGeF)
- Associazione Italiana per la Ricerca sul Cancro
- European Union (EPIC-CVD 7th FP) [279233]
- BBSRC [BB/I025263/1, BB/I025751/1] Funding Source: UKRI
- MRC [MC_UU_12013/2] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1] Funding Source: researchfish
- Medical Research Council [MC_PC_15018, MC_UU_12013/2] Funding Source: researchfish
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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.
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