Construction of a genetic classifier for ASD using gene pathway analysis

A number of genetic investigations in autism spectrum disorders (ASD) have identified single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) that are associated with this neurodevelopmental disorder. However, as research progresses the evidence points to these genetic alterations likely being confined to specific families or populations with their penetrance in larger populations being somewhat lower. This has led researchers to postulate that the genetics of ASD may consist of an additive collection of common genetic variations that when considered in combination with each other are able to explain more of the heritability of the disorder. In addition to taking a more global view of ASD genetics the contribution of these alterations to the clinical landscape of ASD must also be considered. This chapter begins by summarising nongenetic and genetic findings relating to diagnosing or classifying individuals falling within the ASD continuum. We then discuss the utility of using gene pathway analysis to build a genetic classifier for ASD based on our recent published work including strategies to control for population stratification and inclusion of both risk and protective contributors of ASD status. Finally, we will discuss how this approach may be applied to other neuropsychiatric disorders and ways to improve on classification accuracy.