Common genetic risk factors in ASD and ADHD co-occurring families

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two major neurodevelopmental disorders that frequently co-occur. However, the genetic mechanism of the co-occurrence remains unclear. The New Jersey Language and Autism Genetics Study (NJLAGS) collected more than 100 families with at least one member affected by ASD. NJLAGS families show a high prevalence of ADHD and provide a good opportunity to study shared genetic risk factors for ASD and ADHD. The linkage study of the NJLAGS families revealed regions on chromosomes 12 and 17 that are significantly associated with ADHD. Using whole-genome sequencing data on 272 samples from 73 NJLAGS families, we identified potential risk genes for ASD and ADHD. Within the linkage regions, we identified 36 genes that are associated with ADHD using a pedigree-based gene prioritization approach. KDM6B (Lysine Demethylase 6B) is the highest-ranking gene, which is a known risk gene for neurodevelopmental disorders, including ASD and ADHD. At the whole-genome level, we identified 207 candidate genes from the analysis of both small variants and structure variants, including both known and novel genes. Using enrichment and protein-protein interaction network analyses, we identified gene ontology terms and pathways enriched for ASD and ADHD candidate genes, such as cilia function and cation channel activity. Candidate genes and pathways identified in our study improve the understanding of the genetic etiology of ASD and ADHD and will lead to new diagnostic or therapeutic interventions for ASD and ADHD in the future.