New Autism Genes Identified in Largest Study to Date

Autism spectrum disorder (ASD) affects approximately 2.3% of children in the U.S. Although most of the genetic risk of this highly heritable disorder is associated with common variants, with each variant having a small effect and acting additively across the genome, rare and de novo variants confer substantial risk in at least in 10% of cases. The advent of exome sequencing (ES) has allowed for rare coding variants to be studied in ASD and many related developmental and neuropsychiatric disorders. Some individuals with ASD carry pathogenic variants that are rarely observed in the general population, and hundreds of risk genes have been discovered across various neuropsychiatric disorders, with associations driven largely by phenotypic severity and cohort size. During the past decade or so, researchers have studied the strength of gene-specific natural selection against such pathogenic variants and have catalogued them, as well as identified genes that are associated with ASD and other neurodevelopmental disorders (NDDs). However, it has remained unclear as to which genes contribute to clinical features that are more common to ASD compared to other NDDs, what types of genetic variation influence clinical outcomes, and in what periods of development they have the strongest effect on neurodevelopment. Providing the results of the largest genetic analysis to date, a new study now addresses these questions and provides insight into how abnormalities of neurodevelopment arise (Fu et al, 2022). After examining the genomes of more than 150,000 participants, including 20,000 individuals who have been diagnosed with autism, the researchers’ results identified 185 genes associated with autism, many for the first time. The study represents the most comprehensive analysis of the diverse forms of genetic variation in autism and provides new insight into the underlying mechanism of neurodevelopment.