Excess of twins among affected sibling pairs with autism: Implications forthe etiology of autism

It is widely accepted that genes play a role in the etiology of autism. Evi dence for this derives, in part, from twin data. However, despite convergin g evidence from gene-mapping studies, aspects of the genetic contribution r emain obscure. In a sample of families selected because each had exactly tw o 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 o f unknown zygosity) were twin pairs. Deviation from expected values was sta tistically significant (P<10(-6) for all twins); in a similarly ascertained sample of individuals with type I diabetes, there was no deviation from ex pected values. We demonstrate that to ascribe the excess of twins with auti sm solely to ascertainment bias would require very large ascertainment fact ors; for example, affected twin pairs would need to be, on average, <simila r to>10 times more likely to be ascertained than affected nontwin 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 n ongenetic) in the parents may contribute to autism.