The joint effect of air pollution exposure and copy number variation on risk for autism

Abstract

Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P < 0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25-2.73) or ozone (OR 1.20, 95% CI 0.93-1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. Autism Res 2017, 10: 1470-1480. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

A role for gene-environment interactions in Autism Spectrum Disorder is suggested by variants in genes regulating exposure to environmental factors

“…Studies that investigate the interplay between genetic and environmental factors in ASD are sparse. Potential interactions associated with the pathology have been reported for prenatal exposure to PM10 and NO2 and rs1858830 polymorphism on MET gene (116), maternal folic acid intake during gestation and rs1801133 polymorphism on MTHFR (52) and O3 exposure and overall burden of copy number duplications (117). We hypothesize that environmental factors can function as a trigger for ASD onset, only in subjects with a genetic susceptibility.…”

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

“…Chemical exposures-gene interactions that influence risk of psychiatric and neurologic diseases have also been reported. For example, individuals with increased air pollutant or heavy metal exposure and a particular genetic variant have increased risk of neurodevelopmental disorders compared to individuals without the genetic variant, suggesting the genetic variant makes them more susceptible to the chemical exposure [42][43][44][45][46]. Interaction between cigarette smoking and genotype at the PON1 gene locus were observed to influence the risk of bipolar and major depression disorders [47].…”

The current state of the problem of autism spectrum disorders — some biomedical and socio-humanitarian aspects

“…В качестве вклада средовых факторов в развитие РАС рассматривают вирусные инфекции, в частности краснуху и корь, вакцины, продукты питания, фталаты и фенолы, растворители, алкоголь. В последних исследованиях показано, что даже повышенная концентрация в окружающей среде озона способствует более высокому риску развития аутизма [43].…”