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Rosenthal SB, Willsey HR, Xu Y, et al. A convergent molecular network underlying autism and congenital heart disease. Cell Syst. 2021;12(11):1094-1107.e6doi: 10.1016/j.cels.2021.07.009.
Rosenthal, S. B., Willsey, H. R., Xu, Y., Mei, Y., Dea, J., Wang, S., Curtis, C., Sempou, E., Khokha, M. K., Chi, N. C., Willsey, A. J., Fisch, K. M., & Ideker, T. (2021). A convergent molecular network underlying autism and congenital heart disease. Cell systems, 12(11), 1094-1107.e6. https://doi.org/10.1016/j.cels.2021.07.009
Rosenthal, Sara Brin, et al. "A convergent molecular network underlying autism and congenital heart disease." Cell systems vol. 12,11 (2021): 1094-1107.e6. doi: https://doi.org/10.1016/j.cels.2021.07.009
Rosenthal SB, Willsey HR, Xu Y, Mei Y, Dea J, Wang S, Curtis C, Sempou E, Khokha MK, Chi NC, Willsey AJ, Fisch KM, Ideker T. A convergent molecular network underlying autism and congenital heart disease. Cell Syst. 2021 Nov 17;12(11):1094-1107.e6. doi: 10.1016/j.cels.2021.07.009. Epub 2021 Aug 18. PMID: 34411509; PMCID: PMC8602730.
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Cell Syst. 2021 Nov 17;12(11):1094-1107.e6. doi: 10.1016/j.cels.2021.07.009. Epub 2021 Aug 18.

A convergent molecular network underlying autism and congenital heart disease.

Cell systems

Sara Brin Rosenthal, Helen Rankin Willsey, Yuxiao Xu, Yuan Mei, Jeanselle Dea, Sheng Wang, Charlotte Curtis, Emily Sempou, Mustafa K Khokha, Neil C Chi, Arthur Jeremy Willsey, Kathleen M Fisch, Trey Ideker

Affiliations

  1. Center for Computational Biology & Bioinformatics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  2. Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  3. Division of Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  4. Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.
  5. Pediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
  6. Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  7. Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: [email protected].
  8. Center for Computational Biology & Bioinformatics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
  9. Division of Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].

PMID: 34411509 PMCID: PMC8602730 DOI: 10.1016/j.cels.2021.07.009

Abstract

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Subject areas: systems biology; autism; congenital heart disease; network genetics

Conflict of interest statement

Declaration of interests T.I. is co-founder of Data4Cure, is on the Scientific Advisory Board, and has an equity interest. T.I. is on the Scientific Advisory Board of Ideaya BioSciences, has an equity

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