A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk.

A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypothesis have so far failed to explain the large difference in ASD prevalence between the sexes. To address this knowledge gap, we examined sex chromosome aneuploidy in a large ASD case-control cohort to evaluate the relationship between X and Y chromosome dosage and ASD risk.