Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Paula Singmann  1 , Doron Shem-Tov  2 , Simone Wahl  3 , Harald Grallert  3 , Giovanni Fiorito  4 , So-Youn Shin  5 , Katharina Schramm  6 , Petra Wolf  6 , Sonja Kunze  1 , Yael Baran  2 , Simonetta Guarrera  4 , Paolo Vineis  7 , Vittorio Krogh  8 , Salvatore Panico  9 , Rosario Tumino  10 , Anja Kretschmer  1 , Christian Gieger  1 , Annette Peters  11 , Holger Prokisch  6 , Caroline L Relton  5 , Giuseppe Matullo  4 , Thomas Illig  12 , Melanie Waldenberger  1 , Eran Halperin  13
Affiliations

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

Paula Singmann et al. Epigenetics Chromatin. .

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Genome-wide sex differences in DNAm across the autosomes in the discovery study KORA F4 (Manhattan plot). Chromosomes (autosomes) are represented by alternating colors with the lighter color per chromosome representing hypermethylated CpGs and the darker color hypomethylated CpGs (male versus female). The red line represents the significance level of 1.26E−07
Fig. 2
Fig. 2
Correlations between SMAs identified in KORA F4 and the respective associations in each replication study. Each point corresponds to one CpG site. SMAs in the discovery sample KORA F4 are plotted against SMAs in the three replication studies, with a KORA F4 against KORA F3, b KORA F4 against ALSPAC, c KORA F4 against EPICOR. Note that only the CpGs that were significant in KORA F4 and subsequently taken to replication are plotted, which results in the gap in the middle of the graphs
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kim AM, Tingen CM, Woodruff TK. Sex bias in trials and treatment must end. Nature. 2010;465(7299):688–689. doi: 10.1038/465688a. - DOI - PubMed
    1. Tingen CM, Kim AM, Wu P-H, Woodruff TK. Sex and sensitivity: the continued need for sex-based biomedical research and implementation. Womens Health (Lond Engl) 2010;6(4):511–516. doi: 10.2217/whe.10.45. - DOI - PubMed
    1. Mittelstrass K, Ried JS, Yu Z, Krumsiek J, Gieger C, Prehn C, et al. Discovery of sexual dimorphisms in metabolic and genetic biomarkers. PLoS Genet. 2011;7(8):1002215. doi: 10.1371/journal.pgen.1002215. - DOI - PMC - PubMed
    1. Boraska V, Jeroncic A, Colonna V, Southam L, Nyholt DR, Rayner NW, et al. Genome-wide meta-analysis of common variant differences between men and women. Hum Mol Genet. 2012;21(21):4805–4815. doi: 10.1093/hmg/dds304. - DOI - PMC - PubMed
    1. Zhu Z-Z, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L, et al. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol. 2012;41(1):126–139. doi: 10.1093/ije/dyq154. - DOI - PMC - PubMed
-