What constitutes an environmental risk for autism?

June 18, 2014

Following May's publication of the largest-ever population study of autism spectrum disorder, the Simons Foundation sampled opinion from leading ASD researchers on the Swedish authors' contention that half of heritability in ASD is based on genetic factors.

Much of the media coverage following the publication concluded the "other half" of heritability in ASD must be due to environmental factors. Dr. Lonnie Zwaigenbaum, co-lead of NeuroDevNet's ASD research group, participated in an online "Cross-talk" exploration of hertability in autism, and what exactly "environmental causes" might constitute.

The Swedish Study, reported 7 May in The Journal of the American Medical Association was deemed controversial, as other researchers questioned mathematical modeling used in determining risk. The Swedish study found that the risk of autism rises with increasing genetic relatedness to a family member with the disorder.

“The authors provide estimates of autism recurrence risk for each of the types of relatives (from twins, to siblings, half-siblings and cousins), which may be helpful in counseling families," observed Dr. Zwaigenbaum in his Cross-talk commentary. "It is important to note that these risk estimates (for example, 12.9 percent in siblings) are based on risk at age 20 years, in contrast to other recent studies in which recurrence risk was based on assessment at a much younger age. For instance, Sally Ozonoff and her colleagues reported in 2011 that 18.7 percent of younger siblings of children with autism also have the diagnosis at age 3 years.

“It is intriguing that they do not find any trend towards increasing recurrence risk of autism in relatives over the study period," added Dr. Zwaigenbaum. "This is consistent with Danish birth registry data reported last year by Therese Koops Grønborg and her colleagues, despite trends towards higher rates of autism diagnosis in the general community. Such trends are widely regarded to be influenced, at least in part, by the clinical diagnostic criteria for autism broadening over time (that is, to a broader ‘spectrum’). If this is truly the main driver, one might expect to observe trends towards higher recurrence rates as well.

“It’s important to emphasize, though, that heritability estimates do not have a straightforward interpretation for individual families. For example, there are families in which two affected siblings carry different rare pathogenic variants, a circumstance that certainly challenges how we have modeled heritability.”