Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders

Abstract

AbstractDe novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied. We demonstrate that several mutagens, including polycyclic aromatic hydrocarbons (PAHs), disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders (ASD), schizophrenia, and attention deficit hyperactivity disorder (ADHD). Other disease genes including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Our findings support a new paradigm of neurodevelopmental disease etiology driven by a contribution of environmentally induced rather than random mutations.