The genetic and environmental contributions to autism: looking beyond twins.

Abstract

Autism spectrum disorders (ASDs) are serious neurodevelopmental disorders characterized by difficulties in social interaction and communication accompanied by stereotypical, repetitive behavior and restricted interests.1 Once considered rare, ASD is now reported to affect approximately 1% to 2% of children.2,3 The increase in ASD prevalence in recent decades combined with little understanding of ASD etiology have fostered increases in public and private research funding with a substantial investment in genetic research.4 The historical focus on genetic factors partly arose from evidence from the first twin studies5- 7 in which concordance for an ASD diagnosis was reportedly as high as 90% in monozygotic twins and substantially higher than in dizygotic twins. A more recent and larger twin study,8 however, observed a smaller genetic effect and a larger environmental effect on ASD liability than previous work, suggesting that early estimates of the genetic liability for ASD may have been inflated by ascertainment bias.9 Along with twin concordance, another important measure of genetic contribution to disease is familial recurrence. Estimates of sibling recurrence of ASD in families with a previously diagnosed child have ranged from 5.8% to 18.7%,10,11 which are markedly higher than the occurrence of ASD in the general population and thereby support the importance of familial contributions to the risk for ASD.