Excess of twins among affected sibling pairs with autism: implications for the etiology of autism

Am J Hum Genet. 2001 Nov;69(5):1062-7. doi: 10.1086/324191. Epub 2001 Oct 2.


It is widely accepted that genes play a role in the etiology of autism. Evidence for this derives, in part, from twin data. However, despite converging evidence from gene-mapping studies, aspects of the genetic contribution remain obscure. In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ. Of 166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) were twin pairs. Deviation from expected values was statistically significant (P<10(-6) for all twins); in a similarly ascertained sample of individuals with type I diabetes, there was no deviation from expected values. We demonstrate that to ascribe the excess of twins with autism solely to ascertainment bias would require very large ascertainment factors; for example, affected twin pairs would need to be, on average, approximately 10 times more likely to be ascertained than affected non-twin sib pairs (or 7 times more likely if "stoppage" plays a role). Either risk factors (related to twinning or to fetal development) or other factors (genetic or nongenetic) in the parents may contribute to autism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autistic Disorder / etiology*
  • Autistic Disorder / genetics*
  • Bias
  • Diabetes Mellitus, Type 1 / genetics
  • Diseases in Twins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Matched-Pair Analysis
  • Nuclear Family
  • Risk Factors
  • Sex Factors
  • Twins / genetics*
  • Twins, Dizygotic / genetics
  • Twins, Monozygotic / genetics

Associated data

  • OMIM/209850