The Yin and Yang of Autism Genetics: How Rare De Novo and Common Variations Affect Liability

Annu Rev Genomics Hum Genet. 2017 Aug 31;18:167-187. doi: 10.1146/annurev-genom-083115-022647. Epub 2017 Apr 19.


The etiology of autism spectrum disorder (ASD) is complex, involving both genetic and environmental contributions to individual and population-level liability. Early researchers hypothesized that ASD arises from polygenic inheritance, but later results, such as the identification of mutations in certain genes that are responsible for syndromes associated with ASD, led others to propose that de novo mutations of major effect would account for most cases. This yin and yang of monogenic causes and polygenic inheritance continues to this day. The development of genome-wide genotyping and sequencing techniques has resulted in remarkable advances in our understanding of the genetic architecture of risk for ASD. The combined research findings provide solid evidence that ASD is a complex polygenic disorder. Rare de novo and inherited variations act within the context of a common-variant genetic load, and this load accounts for the largest portion of ASD liability.

Keywords: autism; common variants; de novo; genetic architecture.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autism Spectrum Disorder / etiology
  • Autism Spectrum Disorder / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Mutation*
  • Polymorphism, Genetic*