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Interplay of Environmental Pollutants and Folate in the Etiology of Autistic Traits Analysis Using Multipollutant Approaches

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a spectrum of communication deficits and repetitive behaviors. The challenges in learning, thinking, and problem-solving abilities of people with ASD can be debilitating. There is currently no cure for ASD. Many environmental pollutants are suspected to contribute to the etiology of ASD and its associated traits, whereas folate and folate supplements have been shown to exhibit both protective and adjuvant roles. Little is known about the interplay of multiple environmental pollutants and folate in the etiology of ASD. Additionally, statistical approaches that consider the effects of pollutant mixtures instead single pollutant approaches and establishing the appropriate windows of susceptibility of these pollutants are needed when assessing the relationship between environmental pollutants and health outcomes. Methods: In order to examine the interplay between environmental pollutants, folate, and autistic traits, ExWAS (Exposome Wide Association Study), BKMR (Bayesian Kernel Machine regression), and QgComp (Quantile G Computation) were used. These methods consider many of the challenges associated with pollutants mixtures. The data sources used in this study were the NHANES (National Health and Nutrition Examination Survey) and GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort. Results: Many environmental pollutants were inversely associated with decreased folate, and autistic traits. Additionally, many environmental pollutants were both positively and inversely associated with autistic traits, and these associations often depended on sex. Finally, folate did modify the associations between some environmental pollutant mixtures and autistic traits, including phthalates, PFAS, and benzophenones. Conclusions: This study highlights the importance for continued research on the etiology of autism. The novel findings of this study inform future epidemiologic analyses of the importance of sex-specific associations between environmental pollutants and autistic traits, and the importance of pollutant mixtures approaches and nutrients when considering such associations. The exploration of new mechanistic pathways between environmental pollutants and autistic traits through folate opens new avenues for future research. Finally, this dissertation provides further evidence that harmful environmental pollutants remain ubiquitous pollutants and remain a threat to public health. Although the results of this dissertation are modest, population level-influence depends on the magnitude of its impact on health and distribution of the factor. Given the ubiquitous exposure to environmental pollutants these modest effect sizes may have a considerable impact on populations.