Challenge and Potential for Research on Gene-Environment Interactions in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder defined by impairment in social communication and repetitive behaviors. Twin and family studies strongly support a genetic contribution to ASD risk but also indicate an important role for environmental factors, particularly non-shared environmental factors, which can include gene-environment interactions. An accelerating array of research has identified rare genetic risk factors in ASD. Rare prenatal exposures, such as valproic acid or rubella, also suggest a role for uncommon environmental risk factors in ASD. Less robust data support specific common genetic or environmental risk factors. A handful of studies have begun to explore the potential interaction between individual risk factors. Thus far, the most informative approach has been to evaluate potential common factors contributing risk within the context of a rare disorder with a high risk of ASD, such as fragile X syndrome or tuberous sclerosis. Extending beyond this approach will require careful attention to the potential biological relationships between individual risk factors, which may require initial studies in animal models before extending into human populations. Here, we review the initial forays into gene-environment interaction research in ASD and lay out the challenges and opportunities for future research in this important domain.