A convergent molecular network underlying autism and congenital heart disease

Patients with neurodevelopmental disorders, including autism, have an elevated incidence of congenital heart disease, but the extent to which these conditions share molecular mechanisms remains unknown. Here, we use network genetics to identify a convergent molecular network underlying autism and congenital heart disease. This network is impacted by damaging genetic variants from both disorders in multiple independent cohorts of patients, pinpointing 101 genes with shared genetic risk. Network analysis also implicates risk genes for each disorder separately, including 27 previously unidentified genes for autism and 46 for congenital heart disease. For 7 genes with shared risk, we create engineered disruptions in Xenopus tropicalis, confirming both heart and brain developmental abnormalities. The network includes a family of ion channels, such as the sodium transporter SCN2A, linking these functions to early heart and brain development. This study provides a road map for identifying risk genes and pathways involved in co-morbid conditions.

Automated summary

Using network genetics, this study identified a convergent molecular network underlying autism and congenital heart disease, pinpointing 101 genes with shared genetic risk. Additionally, previously unidentified genes for autism and congenital heart disease were implicated, providing insights into the pathological mechanisms of co-morbid conditions. The study also confirmed heart and brain developmental abnormalities in Xenopus tropicalis, highlighting the role of ion channels like SCN2A in early heart and brain development.