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

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, Iftikhar Kullo, Eric B. Larson, Laura J. Rasmussen-Torvik, Daniel J. Schaid, Jordan W. Smoller, Ian B. Stanaway, Wei-Qi Wei, Chunhua Weng and Marylyn D. Ritchie ()
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Xinyuan Zhang: 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
Anurag Verma: University of Pennsylvania
Wendy K. Chung: Columbia University
David Crosslin: University of Washington
Joshua C. Denny: 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

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30678-w

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