Advances and Challenges in the Genetics of Autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, language, and behavioral flexibility. ASD is extremely heterogeneous, with variations among patients observed both in these core behavioral symptoms and in co-occurring medical conditions. Despite its heterogeneity, ASD is among the most heritable of psychiatric disorders. Therefore, genetics offers great promise for determining the causes of ASD. At this time, the utility of clinical testing for ASD is limited. However, recent paradigm shifts in technology and experimental approach have resulted in a new understanding of the genetic contributions to ASD risk. Technological advances allow for the detection of genetic variations on a genome-wide scale with precision that was not possible only 3 years ago. Experimental approaches that include large sample sizes reduce the possibility of spurious results. Several recent reports have implicated genetic regions that may contribute to ASD risk. Linkage studies using large sample sizes identified novel regions of the genome that may harbor rare mutations leading to ASD. Genome-wide association studies revealed chromosomal regions with common functional variants that contribute to ASD susceptibility. Analyses of copy number variations identified rare deletions and duplications of chromosomal regions that may contribute to ASD risk in some individuals. Support for specific ASD candidate genes continues to grow. The application of these technologies points to several new chromosomal regions that contribute to ASD risk. The challenges are now to identify functional genetic variants and to describe the biological impact of the risk alleles on altered brain development.