title: Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders.
abstract: Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexually dimorphic pathways. Here we characterized sexually dimorphic gene expression in multiple data sets from neurotypical adult and prenatal human neocortical tissue, and evaluated ASD risk genes for evidence of sex-biased expression. We find no evidence for systematic sex-differential expression of ASD risk genes. Instead, we observe that genes expressed at higher levels in males are significantly enriched for genes upregulated in post-mortem autistic brain, including astrocyte and microglia markers. This suggests that it is not sex-differential regulation of ASD risk genes, but rather naturally occurring sexually dimorphic processes, potentially including neuron-glial interactions, that modulate the impact of risk variants and contribute to the sex-skewed prevalence of ASD.
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Werling
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Neelroop N
authors.initials: NN
authors.lastname: Parikshak
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.|Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.|Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.|Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D012737:Sex Factors; D059467:Transcriptome; D055815:Young Adult