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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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    as
    1. Xia Shen & Lucija Klarić & Sodbo Sharapov & Massimo Mangino & Zheng Ning & Di Wu & Irena Trbojević-Akmačić & Maja Pučić-Baković & Igor Rudan & Ozren Polašek & Caroline Hayward & Timothy D. Spector & J, 2017. "Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    2. Molly A. Hall & John Wallace & Anastasia Lucas & Dokyoon Kim & Anna O. Basile & Shefali S. Verma & Cathy A. McCarty & Murray H. Brilliant & Peggy L. Peissig & Terrie E. Kitchner & Anurag Verma & Sarah, 2017. "PLATO software provides analytic framework for investigating complexity beyond genome-wide association studies," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    3. Fumihiko Takeuchi & Masato Akiyama & Nana Matoba & Tomohiro Katsuya & Masahiro Nakatochi & Yasuharu Tabara & Akira Narita & Woei-Yuh Saw & Sanghoon Moon & Cassandra N. Spracklen & Jin-Fang Chai & Youn, 2018. "Interethnic analyses of blood pressure loci in populations of East Asian and European descent," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    4. Tanya M. Teslovich & Kiran Musunuru & Albert V. Smith & Andrew C. Edmondson & Ioannis M. Stylianou & Masahiro Koseki & James P. Pirruccello & Samuli Ripatti & Daniel I. Chasman & Cristen J. Willer & C, 2010. "Biological, clinical and population relevance of 95 loci for blood lipids," Nature, Nature, vol. 466(7307), pages 707-713, August.
    5. Genevieve L. Wojcik & Mariaelisa Graff & Katherine K. Nishimura & Ran Tao & Jeffrey Haessler & Christopher R. Gignoux & Heather M. Highland & Yesha M. Patel & Elena P. Sorokin & Christy L. Avery & Gil, 2019. "Genetic analyses of diverse populations improves discovery for complex traits," Nature, Nature, vol. 570(7762), pages 514-518, June.
    6. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
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