Excess of Twins among Affected Sibling Pairs with Autism: Implications for the Etiology of Autism

Abstract

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.

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…[82][83][84][85] It has been discussed that twinning in itself might be a risk factor for the development of autism. 86,87 However, three large-scale epidemiological studies have refuted this idea. [88][89][90] In the four twin studies, pairwise concordance rates in monozygotic (MZ) twins were in the range of 36-96%, and 0-30% in same-sex dizygotic (DZ) twin pairs, resulting in heritability estimates > 90%.…”

Genetic Bases of Stuttering: The State of the Art, 2011

“…In the case of nonidentical twins, similarities between the pair members are taken as a reflection of their common environmental influences. Note, however, that there is evidence that twins appear to be more susceptible to a variety of disorders, such as anorexia nervosa [16] and autism [17] when compared to singletons. Therefore, some cases of stuttering among twins may be yet another manifestation of this general difference between twinning and singletons, thus perhaps somewhat blurring the effect of genetics.…”

Estimated Number of Siblings in Japanese Families with Multiple Birth Children using Two Sets of Census Data: 1990 and 1995

“…Often multiple birth children have additional burdens compared with singletons. Greenberg et al (2001) found a remarkably high proportion of affected twin pairs with autism and that the prevalence of cerebral palsy is higher in multiple births than in singletons (Grether et al, 1992;Petterson et al, 1993; as is the proportion of child abuse (Groothuis et al, 1982;Nelson & Martin, 1985;Tanimura et al, 1990). According to Japanese vital statistics, proportions of low birthweight (LBW) infants in singletons were 5.6% in 1990 and 6.5% in 1995.…”