Genes Linked to ASD, ADHD, Schizophrenia, Obesity, and Type-2 Diabetes Found to Mutate More Significantly than Expected
A new study from researchers at Columbia University and the University of North Carolina suggests that environmental carcinogens may disproportionately mutate neurodevelopmental and metabolic genes, leading to a greater risk of neurodevelopmental diseases such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, obesity, and type-2 diabetes. The current study found that genes mutated by polycyclic aromatic hydrocarbons (PAHs)–a class of chemicals found in tobacco smoke and air pollution–and other environmental carcinogens were overwhelmingly enriched for neurodevelopmental processes. This research points out that the transcriptome of neural tissues, especially neurons, is biased toward longer genes, which makes neurodevelopmental genes particularly sensitive to mutation. The study also found that sequence length was a strong driver of mutability, although other factors may more strongly govern the mutability of protein-coding sequences. To come to these conclusions, the authors analyzed whole genome sequencing datasets of mutations in human induced pluripotent stem cell clonal lines exposed to 12 classes of environmental carcinogens and human lung cancers from individuals living in highly polluted regions. They found that certain mutagens, such as radiation and PAHs, disproportionately mutate genes related to neurodevelopmental disorders like ASD, ADHD and schizophrenia. These findings suggest that environmental factors may play a role in the genetic etiology of neurodevelopmental disorders.
