Emerging Genetic Analyses of Autism Spectrum Disorders: Insights from Common and Rare Variation

Background:  The genetic analysis of autism spectrum disorders (ASDs) is accelerating. Increasing sample sizes are revealing risk factors across the allele frequency spectrum. 

Objectives:  Review genetic influences on ASD across the allele frequency spectrum from common variation through to spontaneously arising variation. 

Methods: Genome-wide association analysis has been performed on over 10,000 cases of ASDs. Whole exome sequencing has been performed on ~5,000 cases of ASDs. We also incorporated frequency information from Exome Aggregation Consortium to refine and strengthen the evidence for association.

Results:  For common variation, substantial increases in sample size have led to the identification of genome-wide significant loci. For rare variation, aggregation efforts to exome sequencing have sharpened our ability to identify significant genetic risk factors.

Conclusions: These studies highlight the importance of taking a comprehensive view of genetic risk and the need to continue increasing sample sizes to build the foundation for understanding the biological mechanisms that drive ASD in the population.