Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders

Introduction De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role environmental carcinogens as drivers causal de in neurodevelopmental disorders is poorly studied. Methods To explore mutation vulnerability disease-associated gene sets, we analyzed publicly available whole genome sequencing datasets human induced pluripotent stem cell clonal lines exposed 12 classes carcinogens, lung cancers from individuals living highly polluted regions. We compared observed rates exposure-induced disease-related sets with expected based on control genes randomly sampled using exact binomial tests. sequence characteristics vulnerability, modeled effects length, expression, percent GC content entire coding sequences multivariate Quasi-Poisson regressions. Results demonstrate that several mutagens, including radiation polycyclic aromatic hydrocarbons, disproportionately mutate related autism spectrum schizophrenia, attention deficit hyperactivity disorder. Other disease amyotrophic lateral sclerosis, Alzheimer’s disease, congenital heart orofacial clefts, coronary artery were generally not mutated more than expected. Longer length was strongly associated elevated sequences. Increased expression decreased rate, but mutability genes. increased Discussion Our findings support possibility disorder genetic etiology partially driven by contribution environment-induced germ line somatic mutations.