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; Marylyn D Ritchie

doi:10.1038/s41467-022-30678-w

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

Nat Commun. 2022 Jun 14;13(1):3428. doi: 10.1038/s41467-022-30678-w.

Authors

Xinyuan Zhang^{1

2}, Anastasia M Lucas¹, Yogasudha Veturi¹, Theodore G Drivas¹, William P Bone^{1

2}, Anurag Verma¹, Wendy K Chung³, David Crosslin⁴, Joshua C Denny^{5

6}, Scott Hebbring⁷, Gail P Jarvik⁴, Iftikhar Kullo⁸, Eric B Larson⁹, Laura J Rasmussen-Torvik¹⁰, Daniel J Schaid¹¹, Jordan W Smoller¹², Ian B Stanaway⁴, Wei-Qi Wei⁶, Chunhua Weng¹³, Marylyn D Ritchie¹⁴

Affiliations

¹ Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
² Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
³ Department of Pediatrics and Medicine, Columbia University, New York, NY, 10032, USA.
⁴ Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, 98109, USA.
⁵ Department of Medicine, Vanderbilt University, Nashville, TN, 37235, USA.
⁶ Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, 37230, USA.
⁷ Center for Human Genetics, Marshfield Clinic, Marshfield, WI, 54449, USA.
⁸ Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, 55905, USA.
⁹ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
¹⁰ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
¹¹ Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
¹² Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
¹³ Department of Biomedical Informatics, Columbia University, New York, NY, 10032, USA.
¹⁴ Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. marylyn@pennmedicine.upenn.edu.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Cardiovascular Diseases* / genetics
Genetic Pleiotropy
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Humans
Nervous System Diseases* / genetics
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding