Autism risk assessment in siblings of affected children using sex-specific genetic scores

SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 × 10-6 and 1.9 × 10-5, respectively).Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism.Autistic disorder is the most severe form of a group of autism spectrum disorders (ASDs) characterized by impairments in social interaction, deficits in verbal and non-verbal communication, restricted interests, and repetitive behaviors [1]. With a prevalence of 1 in 110 children, ASDs are among the most common forms of severe developmental disability [2]. The average recurrence risk of autism in siblings of affected children is approximately 10% [3]. This rate is much higher than the prevalence rate for ASDs in the general population, but lower than would be expected for a highly penetrant mutation in a mend