Autism Spectrum Disorder Genetics and the Search for Pathological Mechanisms

Am J Psychiatry. 2021 Jan 1;178(1):30-38. doi: 10.1176/appi.ajp.2020.20111608.


Recent progress in the identification of genes and genomic regions contributing to autism spectrum disorder (ASD) has had a broad impact on our understanding of the nature of genetic risk for a range of psychiatric disorders, on our understanding of ASD biology, and on defining the key challenges now facing the field in efforts to translate gene discovery into an actionable understanding of pathology. While these advances have not yet had a transformative impact on clinical practice, there is nonetheless cause for real optimism: reliable lists of risk genes are large and growing rapidly; the identified encoded proteins have already begun to point to a relatively small number of areas of biology, where parallel advances in neuroscience and functional genomics are yielding profound insights; there is strong evidence pointing to mid-fetal prefrontal cortical development as one nexus of vulnerability for some of the largest-effect ASD risk genes; and there are multiple plausible paths forward toward rational therapeutics development that, while admittedly challenging, constitute fundamental departures from what was possible prior to the era of successful gene discovery.

Keywords: Autism Spectrum Disorder; Genetics/Genomics; Neurodevelopmental Disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Autism Spectrum Disorder / etiology
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / therapy
  • Genes / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans