Sex-Differential Gene Expression in Developing Human Cortex and Its Intersection With Autism Risk Pathways.

Background: Sex-differential biology may contribute to the consistently male-biased prevalence of autism spectrum disorder (ASD). Gene expression differences between males and females in the brain can indicate possible molecular and cellular mechanisms involved, although transcriptomic sex differences during human prenatal cortical development have been incompletely characterized, primarily due to small sample sizes.

Methods: We performed a meta-analysis of sex-differential expression and co-expression network analysis in 2 independent bulk RNA sequencing datasets generated from cortex of 273 prenatal donors without known neuropsychiatric disorders.

Neural Transcriptomic Analysis of Sex Differences in Autism Spectrum Disorder: Current Insights and Future Directions.

Autism spectrum disorder (ASD) is consistently diagnosed 3 to 5 times more frequently in males than females, a dramatically sex-biased prevalence that suggests the involvement of sex-differential biological factors in modulating risk. The genomic scale of transcriptomic analyses of human brain tissue can provide an unbiased approach for identifying genes and associated functional processes at the intersection of sex-differential and ASD-impacted neurobiology. Several studies characterizing gene expression changes in the ASD brain have been published in recent years with increasing sample size and cellular resolution.