Sex-biased methylome and transcriptome in human prefrontal cortex

Area of Science:

• Neuroscience
• Genomics
• Epigenetics

Background:

• Cognitive performance and brain function exhibit sex-based variations.
• These differences may stem from sex-specific epigenomic and transcriptomic profiles in brain regions like the prefrontal cortex (PFC).

Purpose of the Study:

• To investigate genome-wide DNA methylation and gene expression differences between males and females in the human PFC.
• To explore correlations between DNA methylation and gene expression.
• To identify biological pathways associated with sex-biased gene regulation in the PFC.

Main Methods:

• Analysis of postmortem PFC samples from 32 males and 14 females using Illumina's 450K Methylation and HT-12 v4 Gene Expression BeadChips.
• Application of multiple linear regression, Pearson correlation, and DAVID functional annotation.
• Statistical analyses included nominal P-values and multiple-testing correction (q-values).

Main Results:

• Significant sex differences in DNA methylation were observed across 22,124 CpGs, with 8,357 surviving multiple-testing correction.
• Significant sex differences in gene expression were found in 1,489 genes, with 35 surviving multiple-testing correction.
• A correlation was identified between methylation levels of 585 CpGs and expression of 188 host genes, enriched for pathways related to ribosome function, RNA binding, and protein translation.

Conclusions:

• The human PFC exhibits distinct sex-specific methylomic and transcriptomic profiles.
• Sex-biased DNA methylation and gene expression patterns may contribute to, or result from, differential brain development between sexes.