Although autism spectrum disorder (ASD) is known to aggregate in families, individual risk is poorly understood. Even the heritability of ASD, a broad and seemingly straightforward population measure, is uncertain. In evaluating heritability, several studies have focused on twins, particularly pairs in which at least one twin had a diagnosis of ASD. These studies estimated that the heritability of autism could be as high as 80–90%; however, the most recent twin study, which relied on data from the California Department of Developmental Services, suggested in 2011 that the figure could be as low as 38%.
In hopes of clarifying matters, researchers at Karolinska Institutet in Sweden, King’s College in London, and Mount Sinai in the United States conducted a longitudinal cohort study of all births in Sweden between 1982 and 2006. The study included about 2 million children, 14,516 of which had a diagnosis of autism spectrum disorder. The researchers analyzed pairs of family members: identical and non-identical twins, siblings, and maternal and paternal half-siblings and cousins.
This study not only took in a large number of participants, it also considered a wide variety of familial relationships. Accordingly, the researchers hoped that it would let them answer questions not only about heritability, but also about familial aggregation of ASD. “Our study was prompted by a very basic question which parents often ask: ‘If I have a child with autism, what is the risk my next child will too?,’” said Sven Sandin of the Karolinska Institutet.
In addition to measuring heritability, which is the proportion of risk in the population that can be attributed to genetic factors, the researchers determined relative recurrent risk (RRR), which is the individual risk for people who have a relative with autism.
The results of the study, which will appear May 7 in JAMA, indicate that the heritability of autism is 50%, with the other 50% explained by non-heritable or environmental factors. The study also showed that children with a brother or sister with autism are 10 times more likely to develop autism; 3 times if they have a half-brother or sister; and 2 if they have a cousin with autism.
“Heritability is a population measure, so whilst it does not tell us much about risk at an individual level, it does tell us where to look for causes, said Avi Reichenberg, Ph.D., author of the study and a professor at the Mount Sinai Seaver Center for Autism. “We were surprised by our findings as we did not expect the importance of environmental factors in autism to be so strong.”
The JAMA study, entitled “The Familial Risk of Autism,” explained that while recent research efforts have tended to focus on genes, it now appears more research should focus on identifying environmental factors. Environmental factors are split into “shared environments,” which are shared between family members (such as family socio-economic status), and “non-shared environments,” which are unique to the individual (such as birth complications or maternal infections or medication during the pre and perinatal period).
Factors that are unique to the individual, or non-shared environments, were the major source of environmental risk in the current study.
With respect to RRR, the study "shows that at an individual level, the risk of autism increases according to how close you are genetically to other relatives with autism,” explained Sandin. “We can now provide accurate information about autism risk which can comfort and guide parents and clinicians in their decisions.”