While the decades-long search for genetic causes of autism and autism spectrum disorder (ASD) continues, recent studies looking at twins with autism and at possible causes of the disorders indicate that environmental (non-genetic) factors may play an even larger role than genetics.
In the California Autism Twin Study (CATS)—reportedly the largest population-based twin study of autism to date using contemporary standards for diagnosis—researchers and scientists from 6 academic/research institutions found that shared environmental factors explain about 55% of the liability to autism and 58% of the liability to ASD. This compares with a genetics heritability of 37% for autism and 38% for ASD).1
For the study, twins in which at least 1 twin had a diagnosis of autism or ASD were identified from records of the California Department of Developmental Services (CDDS). Excluded were those with probands of neurogenetic conditions that might account for autism, such as fragile X syndrome or neurofibromatosis.
“What makes our study so different is that we directly assessed the twins,” said Joachim Hallmayer, MD, Associate Professor of Psychiatry and Behavioral Science at Stanford University and principal investigator/director of the study.
Rather than relying on the CDDS reports for diagnosis, the study investigators performed their own evaluations using structured diagnostic as-sessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule), along with parental interviews.
The study also determined twin status through genetic testing—something that was not available when the first twin studies on autism were conducted many years ago.
Funded by grants from the NIMH and Autism Speaks, the study, according to Hallmayer, was undertaken in part because important data were missing about the true autism concordance rate in dizygotic twins.
Three twin studies published between 1977 and 1995, which provided the main body of knowledge on heritability of autism, showed a concordance rate of 72% for a total of 36 monozygotic pairs and a concordance rate of 0% for 30 dizygotic pairs.
“There was grave doubt that the zero rate of concordance in dizygotic twins was correct,” Hallmayer said.
“Our study,” the investigators reported, “provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism overestimated.”
Another aim of the study, Hallmayer told Psychiatric Times, was to further examine the severity of inherited autism. “For example, what happens if one twin is nonverbal, is the other twin nonverbal as well? We need a much more refined analysis of the phenotype and how it is inherited.”
The study included data from 54 monozygotic twins (45 male, 9 female) and 138 dizygotic twins (45 male, 13 female, and 80 sex discordant). Considered demographic factors included twin types, sex, birth weights, and gestational ages, as well as parental ages, education, and ethnicity. The monozygotic twins were slightly older and had shorter gestation periods. The mothers of the dizygotic twins were older than the mothers of the monozygotic twins, “consistent with the known increase in dizygotic twinning with maternal age, and more likely to be white and non-Hispanic,” the investigators reported.