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Inherited genetic factors explain most of the variation in ASD occurrence

Using population data from five countries, researchers estimated that the heritability of autism spectrum disorder was about 80%, indicating that inherited genetic influences contributed to most of the variation in ASD occurrence in the population.

In addition, there was no evidence of contribution from maternal effects, according to the findings published in JAMA Psychiatry.

“Although the origin and development of ASD has been investigated for half a century, it remains controversial,” Sven Sandin, PhD, from the department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, and colleagues wrote.

Using a population-based, multinational cohort design, researchers estimated the additive genetic, maternal and environmental effects in autism spectrum disorder in children from Denmark, Finland, Sweden, Israel and Western Australia who were followed up to age 16 years. Specifically, they fit liability threshold models using structured family data to describe the variance in liability to ASD into additive genetic, maternal, and shared and nonshared environmental components across the five countries.

Of 2,001,631 individuals included in the analysis, 22,156 had diagnosed ASD.

Sandin and colleagues found that the median heritability of autism spectrum disorder was 80.8% (95% CI, 73.2-85.5) for country-specific point estimates, which ranged from 50.9% (95% CI, 25.1-75.6) in Finland to 86.8% (95% CI, 69.8-100) in Israel. In addition, the heritability estimates ranged from 81.2% (95% CI, 73.9-85.3) to 82.7% (95% CI, 79.1-86) in the pooled Nordic sample.

Furthermore, the association between maternal effect, and variation in risk for ASD was minimal, ranging from 0.4% to 1.6%, according to the results.

“The importance of this finding lies in the insight it provides for understanding the risk factors associated with ASD,” the researchers explained. “The absence of [maternal] effects indicates that there is no strong evidence of a maternal effect, driven by genetic factors shared between sisters, associated with the risk of ASD.”

The results also showed that estimates of genetic, maternal and environmental effects for autistic disorder were similar to those for ASD.

Overall, shared environmental factors contributed minimally to ASD risk; however, the Finland and Western Australia samples supported shared environmental influences. Sandin and colleagues explained that population-level differences may explain some of the variation.

“The results suggest possible modest differences in the sources of ASD risk between countries,” they wrote. “The contributions of gene-environment interactions or correlations between genes and environment to ASD risk are important unanswered questions.”

Although the environment seemed to contribute less to the risk for ASD than genetics, potential environmental risk factors usually receive more public and media attention, Amandeep Jutla, MD, from the department of psychiatry, Columbia University, and colleagues wrote in a related editorial.

“Perhaps this is because environmental risk factors, at least in principle, are modifiable. Even with a smaller contribution to risk, it is worthwhile to enrich understanding of environmental risk factors, which remain relatively understudied,” they wrote. “Some identified risk factors, such as preterm birth or birth complications, are already targets of public health efforts for other reasons. Others, such as a shortened interpregnancy interval or an infection during pregnancy, may also be modifiable if the underlying risk mechanisms can be better understood.” – by Savannah Demko

Disclosures: Sandin reported grants from NIH and being a Faculty Fellow of the Beatrice and Samuel A. Seaver Foundation. Please see the study for all other authors’ relevant financial disclosures. Jutla reports support from the Whitaker Scholar in Developmental Neuropsychiatry Award. Please see the editorial for all other authors’ relevant financial disclosures.