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Singmann P, Shem-Tov D, Wahl S, et al. Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenetics Chromatin. 2015;8:43doi: 10.1186/s13072-015-0035-3.
Singmann, P., Shem-Tov, D., Wahl, S., Grallert, H., Fiorito, G., Shin, S. Y., 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, C. L., Matullo, G., Illig, T., Waldenberger, M., & Halperin, E. (2015). Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenetics & chromatin, 843. https://doi.org/10.1186/s13072-015-0035-3
Singmann, Paula, et al. "Characterization of whole-genome autosomal differences of DNA methylation between men and women." Epigenetics & chromatin vol. 8 (2015): 43. doi: https://doi.org/10.1186/s13072-015-0035-3
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. Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenetics Chromatin. 2015 Oct 19;8:43. doi: 10.1186/s13072-015-0035-3. eCollection 2015. PMID: 26500701; PMCID: PMC4615866.
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Epigenetics Chromatin. 2015 Oct 19;8:43. doi: 10.1186/s13072-015-0035-3. eCollection 2015.

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

Epigenetics & chromatin

Paula Singmann, Doron Shem-Tov, Simone Wahl, Harald Grallert, Giovanni Fiorito, So-Youn Shin, Katharina Schramm, Petra Wolf, Sonja Kunze, Yael Baran, Simonetta Guarrera, Paolo Vineis, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Anja Kretschmer, Christian Gieger, Annette Peters, Holger Prokisch, Caroline L Relton, Giuseppe Matullo, Thomas Illig, Melanie Waldenberger, Eran Halperin

Affiliations

  1. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
  2. Blavatnik School of Computer Science, Tel-Aviv University, Tel-Aviv, Israel.
  3. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  4. Human Genetics Foundation-Torino, Turin, Italy ; Department of Medical Sciences, University of Torino, Turin, Italy.
  5. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK ; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  6. Institute of Human Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; Institute of Human Genetics, Technical University Munich, Munich, Germany.
  7. Human Genetics Foundation-Torino, Turin, Italy ; Epidemiology and Public Health, Imperial College London, London, UK.
  8. Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale Tumori, Milan, Italy.
  9. Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
  10. Cancer Registry and Histopathology Unit, "Civile-M.P. Arezzo" Hospital, ASP 7, Ragusa, Italy.
  11. Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  12. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany ; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany ; Institute for Human Genetics, Hannover Medical School, Hannover, Germany.
  13. Blavatnik School of Computer Science, Tel-Aviv University, Tel-Aviv, Israel ; Department of Molecular Microbiology and Biotechnology, George Wise Faculty of Life Science, Tel-Aviv University, Tel-Aviv, Israel ; International Computer Science Institute, Berkeley, CA USA.

PMID: 26500701 PMCID: PMC4615866 DOI: 10.1186/s13072-015-0035-3

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.

Keywords: ALSPAC; CpG; DNA methylation; EPICOR; EWAS; Enrichment analysis; Imprinting; KORA; Sex

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