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mTADA is a framework for identifying risk genes from de novo mutations in multiple traits

Author

Listed:
  • Tan-Hoang Nguyen

    (Icahn School of Medicine at Mount Sinai
    Virginia Commonwealth University)

  • Amanda Dobbyn

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Ruth C. Brown

    (Virginia Commonwealth University)

  • Brien P. Riley

    (Virginia Commonwealth University)

  • Joseph D. Buxbaum

    (Icahn School of Medicine at Mount Sinai)

  • Dalila Pinto

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Shaun M. Purcell

    (Harvard Medical School)

  • Patrick F. Sullivan

    (University of North Carolina)

  • Xin He

    (University of Chicago
    University of Chicago)

  • Eli A. Stahl

    (Icahn School of Medicine at Mount Sinai
    Broad Institute of MIT and Harvard)

Abstract

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. Studies of neuropsychiatric disorders and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios have reported multiple putatively causal genes. However, a joint analysis method designed to integrate DNMs from multiple studies has yet to be implemented. We here introduce multiple-trait TADA (mTADA) which jointly analyzes two traits using DNMs from non-overlapping family samples. We first demonstrate that mTADA is able to leverage genetic overlaps to increase the statistical power of risk-gene identification. We then apply mTADA to large datasets of >13,000 trios for five neuropsychiatric disorders and CHD. We report additional risk genes for schizophrenia, epileptic encephalopathies and CHD. We outline some shared and specific biological information of intellectual disability and CHD by conducting systems biology analyses of genes prioritized by mTADA.

Suggested Citation

  • Tan-Hoang Nguyen & Amanda Dobbyn & Ruth C. Brown & Brien P. Riley & Joseph D. Buxbaum & Dalila Pinto & Shaun M. Purcell & Patrick F. Sullivan & Xin He & Eli A. Stahl, 2020. "mTADA is a framework for identifying risk genes from de novo mutations in multiple traits," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16487-z
    DOI: 10.1038/s41467-020-16487-z
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