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Meta-analysis of human methylation data for evidence of sex-specific autosomal patterns

Citation

McCarthy, NS and Melton, PE and Cadby, G and Yazar, S and Franchina, M and Moses, EK and Mackey, DA and Hewitt, A, Meta-analysis of human methylation data for evidence of sex-specific autosomal patterns, BMC Genomics, 15 Article 981. ISSN 1471-2164 (2014) [Refereed Article]


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Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1186/1471-2164-15-981

Abstract

BACKGROUND: Several individual studies have suggested that autosomal CpG methylation differs by sex both in terms of individual CpG sites and global autosomal CpG methylation. However, these findings have been inconsistent and plagued by spurious associations due to the cross reactivity of CpG probes on commercial microarrays. We collectively analysed 76 published studies (n = 6,795) for sex-associated differences in both autosomal and sex chromosome CpG sites.

RESULTS: Overall autosomal methylation profiles varied substantially by study, and we encountered substantial batch effects. We accounted for these by conducting random effects meta-analysis for individual autosomal CpG methylation associations. After excluding non-specific probes, we found 184 autosomal CpG sites differentially methylated by sex after correction for multiple testing. In line with previous studies, average beta differences were small. Many of the most significantly associated CpG probes were new. Of note was differential CpG methylation in the promoters of genes thought to be involved in spermatogenesis and male fertility, such as SLC9A2, SPESP1, CRISP2, and NUPL1. Pathway analysis revealed overrepresentation of genes differentially methylated by sex in several broad Gene Ontology biological processes, including RNA splicing and DNA repair.

CONCLUSIONS: This study represents a comprehensive analysis of sex-specific methylation patterns. We demonstrate the existence of sex-specific methylation profiles and report a large number of novel DNA methylation differences in autosomal CpG sites between sexes.

Item Details

Item Type:Refereed Article
Keywords:Methylation, Genome, Sex, CpG, Illumina Infinium HumanMethylation27K, Meta- analysis
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
UTAS Author:Mackey, DA (Professor David Mackey)
UTAS Author:Hewitt, A (Professor Alex Hewitt)
ID Code:112592
Year Published:2014
Web of Science® Times Cited:30
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-11-17
Last Modified:2017-11-07
Downloads:118 View Download Statistics

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