A study published in *Nature* (2014) investigates the genetic basis of autism spectrum disorder (ASD), identifying 22 autosomal genes disrupted by de novo loss-of-function mutations, and a larger set of 107 genes enriched for those likely to affect risk. These genes are involved in synaptic, transcriptional, and chromatin remodeling pathways, including voltage-gated ion channels, histone-modifying enzymes, and chromatin remodelers. The study used whole-exome sequencing (WES) on 3,871 ASD cases and 9,937 controls, revealing that de novo mutations in these genes are common in ASD subjects. The analysis also identified 33 genes with a false discovery rate (FDR) < 0.1 and 107 genes with an FDR < 0.3, many of which are known or strongly suspected ASD risk genes. The study further found that these genes are under strong evolutionary constraint, suggesting they are critical for normal brain development. The research highlights the importance of integrating de novo, inherited, and case-control data to identify ASD risk genes. It also shows that many ASD risk genes are involved in synaptic function, chromatin remodeling, and transcriptional regulation. The study concludes that ASD is a complex disorder with a large number of genes involved, and that understanding the genetic architecture of ASD can provide insights into the neurobiology of the disorder and the mechanisms underlying social behavior. The findings suggest that disruptions in synaptic function and chromatin remodeling may contribute to the development of ASD. The study also identifies several new ASD risk genes, including ASH1L, MLL3, and MYO9B, and highlights the role of de novo mutations in ASD. The research underscores the importance of large-scale genetic studies in identifying the genetic basis of ASD and in understanding the molecular mechanisms underlying the disorder.A study published in *Nature* (2014) investigates the genetic basis of autism spectrum disorder (ASD), identifying 22 autosomal genes disrupted by de novo loss-of-function mutations, and a larger set of 107 genes enriched for those likely to affect risk. These genes are involved in synaptic, transcriptional, and chromatin remodeling pathways, including voltage-gated ion channels, histone-modifying enzymes, and chromatin remodelers. The study used whole-exome sequencing (WES) on 3,871 ASD cases and 9,937 controls, revealing that de novo mutations in these genes are common in ASD subjects. The analysis also identified 33 genes with a false discovery rate (FDR) < 0.1 and 107 genes with an FDR < 0.3, many of which are known or strongly suspected ASD risk genes. The study further found that these genes are under strong evolutionary constraint, suggesting they are critical for normal brain development. The research highlights the importance of integrating de novo, inherited, and case-control data to identify ASD risk genes. It also shows that many ASD risk genes are involved in synaptic function, chromatin remodeling, and transcriptional regulation. The study concludes that ASD is a complex disorder with a large number of genes involved, and that understanding the genetic architecture of ASD can provide insights into the neurobiology of the disorder and the mechanisms underlying social behavior. The findings suggest that disruptions in synaptic function and chromatin remodeling may contribute to the development of ASD. The study also identifies several new ASD risk genes, including ASH1L, MLL3, and MYO9B, and highlights the role of de novo mutations in ASD. The research underscores the importance of large-scale genetic studies in identifying the genetic basis of ASD and in understanding the molecular mechanisms underlying the disorder.