Genetic factors account for the bulk of autism risk, but environmental factors are also implicated in risk. Environmental factors are hypothesized to increase risk by pushing a genetically sensitized background over a ‘liability’ threshold, analogous to how common inherited variants additively increase risk. However, whether known environmental risks for autism actually influence phenotype severity in an already genetically sensitized background is currently unknown.
In this pilot project, Mark Zylka’s laboratory will directly test the hypothesis that a combination of environmental and genetic risk produces behavioral phenotypes that are more severe than those seen with only genetic or environmental risk exposure. To do so, Zylka’s team will take advantage of Chromodomain helicase DNA binding protein 8 (Chd8) mutant mice, an established genetic model of autism, and assess the effects of exposure to a known autism environmental risk factor in these animals. Specifically, as prenatal exposure to class II pyrethroids is epidemiologically linked to autism risk, , the effects of prenatal exposure to a class II pyrethroid will be assessed in Chd8 mutant mice. Pyrethroids are a group of pesticides that are frequently found in the home, and pyrethroid metabolites have been reported in human blood and urine, including in pregnant women. Unlike genetic variants, pyrethroid exposure can be minimized or eliminated, particularly during critical periods of brain development. The results of this research could therefore identify an avoidable environmental risk for a common genetic subtype of autism.
