Autism spectrum disorders are among the most heritable common disorders and show extensive clinical heterogeneity, however, both the underlying neurobiological basis and genetic architecture are poorly understood. Four times as many males as females are affected, for unknown reasons. Knowledge about the primary genetic and hormonal determinants of sexual dimorphism may be able to be leveraged in order to dissect a major source of heterogeneity in autism. The objective of this proposal is to investigate genetic causes for increased male risk of autism. Guided by preliminary data including sex-specific genetic contributors to autism and extensive sexually dimorphic genetic architecture for numerous human traits, this proposal comprises a pilot study to recruit subjects, including an enriched female-affected family sample, and compare males and females in order to identify sex-specific susceptibility genes. The results will be significant, as information about what protects females from developing autism could lead to reduction of male risk. The long-term goal is to use genetic tools to better understand the biological basis of autism, leading to advances in diagnosis, prevention and treatment.