Letter to the Editor

Molecular Autism

, 4:10

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Sex-biased gene expression in the developing brain: implications for autism spectrum disorders

  • Mark N ZiatsAffiliated withNational Institute of Child Health and Human Development, National Institutes of HealthNIH – University of Cambridge Biomedical Scholars Program, Robinson CollegeBaylor College of Medicine MSTP, One Baylor Plaza Email author 
  • , Owen M RennertAffiliated withNational Institute of Child Health and Human Development, National Institutes of Health


Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specific mechanistic processes. We discovered that male-biased genes are enriched for the processes of extracellular matrix formation/glycoproteins, immune response, chromatin, and cell cytoskeleton. We highlight that these pathways have been repeatedly implicated in autism and demonstrate that autism candidate genes are also enriched for these pathways. We propose that the overlap of these male-specific brain transcriptional modules with the same pathways in autism spectrum disorders may partially explain the increased incidence of autism in males.


Autistic disorder Gene expression Sex differences