De Novo Variants in Chinese Asd Trios Reveal Distinct Genetic Basis Underlying Autism with and Without Developmental Delay

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder causing social communication and stereotypical behavioral impairments, often with developmental delay or intellectual disabilities (DD/ID). Here, we performed whole-exome sequencing on 772 Chinese ASD trios, combining with a previous 369 ASD trios, to identify de novo variants in 1141 ASD trios. We found that ASD without DD/ID carried less disruptive de novo variants than ASD with DD/ID. Surprisingly, we found that expression of genes with de novo variants in ASD without DD/ID were enriched in a subtype of human neural progenitor cells. Importantly, some ASD risk genes identified in this study are not present in the current ASD gene database, suggesting that there are ubique genetic contributors to ASD in East Asian populations. Together, this work nominates novel ASD risk genes and indicates that ASD genetic studies in different geographic populations are essential to reveal the comprehensive genetic architecture of ASD.