New Willsey Lab study investigates the shared biological underpinnings of autism and congenital heart disease

In collaboration with Trey Ideker’s lab at UCSD and Mustafa Khokha’s lab at Yale, we used network genetics to identify a convergent molecular network underlying autism and congenital heart disease, two co-morbid disorders with shared genetic risk. This network is impacted by damaging genetic variants from both disorders in multiple independent cohorts of patients, pinpointing 101 genes with shared genetic risk–many of which are novel to one or both disorders, thereby providing new clues for understanding these conditions. The network implicates a large family of ion channels, including the sodium transporter SCN2A, in which the authors show disruptions cause. unexpected defects in Xenopus heart and brain development. While sodium channels like SCN2A would typically be ascribed a postnatal role in action-potential neuronal physiology or cardiac rhythm, our results suggest earlier expression and function during embryonic development. Such a developmental role has implications for pathobiology and the timing of gene therapy approaches, and also underscores the challenges of leaning too heavily on gene ontology annotations, which are incomplete and do not capture pleiotropy effectively.

Full text available at Cell Systems.

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