Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication…

• NS
  National Science Foundation

  Award: 2017240332
• AS
  Autism Science Foundation
• JA
  Japan Agency for Medical Research and Development

  Award: JP19dm0107087
• BA
  Beatrice and Samuel A. Seaver Foundation
• SF
  Simons Foundation Autism Research Initiative
• NI
  National Institutes of Health
• UO
  University of California, San Francisco
• NI
  National Institute of Mental Health

  Awards: MH109900, MH100233, MH111662, MH111660, MH111658, MH057881, MH111661, MH115957
• NH
  National Human Genome Research Institute

  Awards: HG008895, HG002295