A rigorous study of nearly 400 twins has shown that environmental factors have been underestimated, and genetics overestimated, for their roles in autism spectrum disorders.
The study found that the children's environment represents more than half of the susceptibility, 55 percent in the most severe form of autism and 58 percent in the broad spectrum of the disorder, while genetics is involved in 37 percent and 38 percent of the risk, respectively.
This is the largest and most rigorous twin study to date to research the genetic component of the disorder, and tapped expertise from the UCSF Institute for Human Genetics and Stanford University which jointly led the research as well as from Kaiser Permanente, UC Davis, the Autism Genetic Research Exchange and the California Department of Public Health.
Autism had been thought to be the most heritable of all neurodevelopmental disorders, with a few small twin studies suggesting a 90 percent link,? said UCSF geneticist Neil Risch, director of the UCSF Institute for Human Genetics and senior author of the paper. It turns out the genetic component still plays an important role, but in our study, it was overshadowed by the environmental factors shared by twins." Our work suggests that the role of environmental factors has been underestimated, said Dr. Joachim Hallmayer, first author of the paper and an associate professor of psychiatry and behavioral sciences at Stanford University.
What exactly those environmental factors are, Hallmayer said, is the multimillion dollar question, but he noted that the disorder's manifestation in very young children indicates a cause early in life and possibly during pregnancy.
Rich and Hallmayer collaborated with autism expert Lisa Croen at Kaiser permanente and epidemiologist Judith Grether at the California Department of Public Health, which tracks autism statewide through records from the Department of Developmental Services. The twin study compared those records with California birth certificates for children born between 1987 and 2004, and identified 2,312 twins in which at least one member was affected with some form of autism. The children were all at least 4 years old, when autism can be really diagnosed.
Hallmayer then worked with UC Davis clinical psychologist Sally Ozonoff and the Southern California-based Autism Genetic Research Exchange to conduct parent interviews and full medical and behavioral evaluations of each child, to systematically assess whether the children had autism spectrum disorder, and if so, at what level of severity. Ultimately, the group was winnowed to 192 pairs of twins, of which 54 were identical and 138 fraternal, for statistical analysis. Since autism disproportionately affects boys, only 80 of the pairs included both sexes.
The results were staggering: A boy with a fraternal twin with autism spectrum disorder had a 31 percent chance of also having the disorder, while a boy with an identical twin with the disorder had a 77 percent chance of sharing it. Both rates are dramatically higher than the general population in which the overall incidence of autism is about 0.6 percent. The high fraternal rate was especially unexpected, Rish said, because fraternal twins has previously been thought to have the same concordance as non-twin siblings. Identical twins share all of their genetic material, while fraternal twins share only half, the same as any siblings. The strong fraternal-twin rate in this study is considerably higher than non-twin siblings, indicating strong environmental component unique to twins.
"The difference between the identical and fraternal rates shows that genetics definitely plays a role in the disorder", Risch said, noting that if it didn't, the concordance rates would be equal among the identical and fraternal groups. "But the fact that the fraternal twins have such a high rate shows that their shared environment is contributing significantly to their susceptibility".
Croen, who is director of the Autism Research Program at Kaiser, said that the findings suggest that events during pregnancy should be a focus for future research into the origins of autism.
The research was funded by the National Institute of Mental Health, one of 27 institutes and centers of the National Institutes of Health, and by Autism Speaks.
Findings appear in the July 2011 issue of the Archives of General Psychiatry and can be found online at http://archpsyc.ama-assn.org