Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders Academic Article uri icon


MeSH Major

  • Autism Spectrum Disorder
  • Genetic Variation
  • Multifactorial Inheritance


  • Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.


publication date

  • July 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5552240

Digital Object Identifier (DOI)

  • 10.1038/ng.3863

PubMed ID

  • 28504703

Additional Document Info

start page

  • 978

end page

  • 985


  • 49


  • 7