Interaction between manganese and GSTP1 in relation to autism spectrum disorder while controlling for exposure to mixture of lead, mercury, arsenic, and cadmium

•Children with BMC≥12 μg/L and GSTP1 Ile/Ile genotype have 4 times higher odds of ASD.•Humans are also exposed to mixtures of other metals such as Pb, Hg, As, and Cd.•Generalized weighted quantile sum was used to control for mixture of these 4 metals.•Interaction between GSTP1 and BMC was significant after adjusting for the mixture. We previously reported a significant interactive association between polymorphisms of GSTP1 and blood manganese concentrations (BMC) with autism spectrum disorder (ASD) in Jamaican children. In this paper, we investigate the same interactive association with ASD while adjusting for the mixture of four metals (lead, mercury, cadmium, and arsenic). We used data from 163 case-control pairs of children 2–8 years of age from our autism project in Jamaica, in which we collected blood for heavy metals analysis at enrollment. To minimize potential multicollinearity between concentrations of the four metals, we generated a mixture index using generalized weighted quantile sum regression, which was used in conditional logistic regression models to control for the four metals while assessing the interactive association between GSTP1 and BMC with ASD. Similar to the findings we reported previously, we found that in co-dominant and dominant models for GSTP1, among children with the Ile/Ile genotype, those with BMC ≥ 12 μg/L had 4.6 and 4.27 times higher odds of ASD compared to those with BMC