Sex-biased methylome and transcriptome in human prefrontal cortex
Open accessAbstract
Brain function and cognitive performance differ between men and women in some measures. The phenotypic variation may be partially due to sex differences in epigenomes and transcriptomes in specific brain regions [e.g. the prefrontal cortex (PFC)]. Genome-wide DNA methylation and gene expression were examined in postmortem PFC of 32 males and 14 females (all were Caucasians) using Illumina's 450K Methylation and HT-12 v4 Gene Expression BeadChips, respectively. Multiple linear regression, Pearson correlation and DAVID functional annotation analyses were applied to investigate sex-biased DNA methylation and gene expression, DNA methylation-gene expression correlation and gene ontology (GO) annotations overrepresented by differentially methylated and expressed genes. A total of 22 124 CpGs showed differential methylation between males and females (2.6 × 10(-38) ≤ Pnominal ≤ 0.05), and the P-values of 8357 CpGs withstood multiple-testing correction (q < 0.05). A total of 1489 genes showed differential expression between males and females (4.1 × 10(-36) ≤ Pnominal ≤ 0.05), and the P-values of 35 genes survived multiple-testing correction (q < 0.05). A significant correlation (Pcorrelation < 0.05) was observed between methylation levels of 585 differentially methylated CpGs (Pnominal ≤ 0.05) and expression levels of 188 differentially expressed host genes (Pnominal < 0.05). The GO terms enriched by these 188 genes (134 on autosomes and 54 on sex chromosomes) were assigned to 24 clusters, and 33 genes involved in the top cluster (enrichment score: 4.7) mainly participate in ribosome structure and function, RNA binding and protein translation. This study demonstrated sex-specific methylomic and transcriptomic profiles in the human PFC. Our findings suggest that sex-biased DNA methylation and gene expression could be either the cause or consequence of differential brain development between males and females.
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DNA methylation profiles differ significantly between males and females at many loci in adult brains.
“DNA methylation profiles differ significantly between males and females at many loci in adult brains [17]”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [17]
Among 451 unique CpGs identified in our sex-stratified analysis or sex-by-Braak stage interaction analysis, only 16 were also identified in Xia et al. and none were identified in Xu et al.
“Among 451 unique CpGs identified in our sex-stratified analysis or sex-by-Braak stage interaction analysis, only 16 were also identified in Xia et al. [16] and none were identified in Xu et al. [17]”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [17]
The comparison with Xia et al. and Xu et al. showed our results were largely distinct.
“The comparison with Xia et al. [16] and Xu et al. [17], which examined differential methylation between males and females in the prefrontal cortex, but without considering AD neuropathology [16, 17], showed our results were largely distinct.”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [17]
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“identified genes with differential methylation between males and females in the brain prefrontal cortex and found that many of these genes participate in protein synthesis [33] and overlap with genes and pathways involved in psychiatric disorders (autism, depression, and schizophrenia) [34].”
Background
- Authors
- Xu, H., Wang, F., Liu, Y., Yu, Y., Gelernter, J., & Zhang, H.
- Affiliations
- Jilin University (CN)
- VA Connecticut Healthcare System (US)
- Yale University (US)
- Corresponding author
- Zhang, Huiping
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-24
- Volume
- 23
- Issue
- 5
- Pages
- 1260-1270
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3919013
- OpenAlex
- W2136178470
- Cited by
- 151
- References
- 4
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 19 · 2021: 18 · 2020: 20 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 13 · 2015: 16 · 2014: 6
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Sydney
- National Institutes of Health (K99-R00)
- Medical Research Council
- National Health and Medical Research Council
- National Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (P50 AA12870, AA 12870, P50AA012870, R28AA012725)
- National Institute on Drug Abuse (K99/R00 DA022891, R00DA022891)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- sex differences, DNA methylation, gene expression, prefrontal cortex, epigenome, transcriptome, differentially methylated CpGs, sex chromosomes, ribosome structure, RNA binding, mRNA translation, brain development, postmortem brain
- MeSH terms
- Aged, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Sex Factors, Cluster Analysis, Prefrontal Cortex, CpG Islands, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Genome-Wide Association Study, Transcriptome
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