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Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders

Author

Listed:
  • Xinyuan Zhang

    (University of Pennsylvania
    University of Pennsylvania)

  • Anastasia M. Lucas

    (University of Pennsylvania)

  • Yogasudha Veturi

    (University of Pennsylvania)

  • Theodore G. Drivas

    (University of Pennsylvania)

  • William P. Bone

    (University of Pennsylvania
    University of Pennsylvania)

  • Anurag Verma

    (University of Pennsylvania)

  • Wendy K. Chung

    (Columbia University)

  • David Crosslin

    (University of Washington)

  • Joshua C. Denny

    (Vanderbilt University
    Vanderbilt University)

  • Scott Hebbring

    (Center for Human Genetics, Marshfield Clinic)

  • Gail P. Jarvik

    (University of Washington)

  • Iftikhar Kullo

    (Mayo Clinic)

  • Eric B. Larson

    (Kaiser Permanente Washington Health Research Institute)

  • Laura J. Rasmussen-Torvik

    (Northwestern University Feinberg School of Medicine)

  • Daniel J. Schaid

    (Department of Health Sciences Research, Mayo Clinic)

  • Jordan W. Smoller

    (Massachusetts General Hospital)

  • Ian B. Stanaway

    (University of Washington)

  • Wei-Qi Wei

    (Vanderbilt University)

  • Chunhua Weng

    (Columbia University)

  • Marylyn D. Ritchie

    (University of Pennsylvania)

Abstract

Clinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. However, genetic susceptibility factors shared between these disease categories remain largely unknown. Here, we characterized pleiotropy across 107 circulatory system and 40 nervous system traits using an ensemble of methods in the eMERGE Network and UK Biobank. Using a formal test of pleiotropy, five genomic loci demonstrated statistically significant evidence of pleiotropy. We observed region-specific patterns of direction of genetic effects for the two disease categories, suggesting potential antagonistic and synergistic pleiotropy. Our findings provide insights into the relationship between circulatory system diseases and nervous system disorders which can provide context for future prevention and treatment strategies.

Suggested Citation

  • Xinyuan Zhang & Anastasia M. Lucas & Yogasudha Veturi & Theodore G. Drivas & William P. Bone & Anurag Verma & Wendy K. Chung & David Crosslin & Joshua C. Denny & Scott Hebbring & Gail P. Jarvik & Ifti, 2022. "Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30678-w
    DOI: 10.1038/s41467-022-30678-w
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