Excess of twins among affected sibling pairs with autism: implications for the etiology of autism.
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.
Greenberg
D A
DA
Division of Statistical Genetics, Department of Biostatistics, Columbia University and New York State Psychiatric Institute, New York, NY 10032, USA. dag@shallot.salad.mssm.edu
Hodge
S E
SE
Sowinski
J
J
Nicoll
D
D
D001321:Autistic Disorder / Q000209:etiology* / Q000235:genetics*; D015982:Bias; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D009679:Nuclear Family; D012307:Risk Factors; D012737:Sex Factors; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics