An Integrative Molecular Concept Modeling of GxE Interactions in Autism

Background: Over the last decade autism has emerged as a major pandemic affecting 1 out of 160 children in the. Autism is a behaviorally defined syndrome that is diagnosed on the basis of clinical history. Currently there are no known genetic markers. Diagnostic criteria include presence before the age of three of language impairment, social reciprocity deficits and a tendency to engage in repetitive behavior. Family and twin studies have firmly established the roles of genes and environment in autism. Despite this knowledge defining the genetic architecture of autism spectrum disorder (ASD) remains a central challenge. One of the more significant bottlenecks is the inability to conduct research that incorporates gene by environment interactions in study designs and analysis strategies.

Objectives: To determine whether autism candidate genes are functionally related and interact with environmental response genes within pathways.

Methods: We performed pathway prediction and network modeling to elucidate GxE interactions at molecular level. We hypothesized that autism candidate genes and environment response genes interact within pathways, and are functionary related. We used 238 autism candidate genes identified through knowledge discovery, and 654 environment response genes from the Environmental Genome Project to test this hypothesis.

Results: We have shown that autism candidate genes and environment genes are functionally related and interact within pathways. Among the sets of genes identified include the interleukins.

Conclusions: This analysis reveals complex interactions and highlights the potential role of environment in gene regulation and function.