Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

Abstract

The exome sequences of approximately 8,000 children with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) and 5,000 controls were analyzed, finding that individuals with ASD and individuals with ADHD had a similar burden of rare protein-truncating variants in evolutionarily constrained genes, both significantly higher than controls. This motivated a combined analysis across ASD and ADHD, identifying microtubule-associated protein 1A (MAP1A) as a new exome-wide significant gene conferring risk for childhood psychiatric disorders. Using samples from the Danish Neonatal Screening Biobank, children with ASD and children with ADHD were found to have similar, significantly increased rates of rare protein-truncating variants in evolutionarily constrained genes.