The genetics of autism: key issues, recent findings, and clinical implications

Abstract

Autism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding opportunities for the development of novel treatments and understanding of their natural history. Although the underlying genetic architecture of ASDs is not yet known, the literature demonstrates that it is not a monogenic disorder with mendelian inheritance, rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. This article reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of common and rare variant discoveries.

Figure 1

This graph illustrates the anticipated relationship between allele frequency and effect size for both common and rare disorders. Mendelian (or simple genetic) syndromes fall to the left-most aspect of the x-axis. To date, most genome-wide association studies across all of medicine have demonstrated that common alleles carry very small risks (far right side of the graph). Recent findings with regard to common risk variants in ASD have followed this pattern. Many of the rare mutations so far identified in ASD, appear to fall somewhere in the middle of this figure, showing low allele frequency and effect sizes that are not as great as those found in single gene disorders.