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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	3428
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30678-w
State	Published - Dec 2022

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Zhang, X., Lucas, A. M., Veturi, Y., Drivas, T. G., Bone, W. P., Verma, A., Chung, W. K., Crosslin, D., Denny, J. C., Hebbring, S., Jarvik, G. P., Kullo, I., Larson, E. B., Rasmussen-Torvik, L. J., Schaid, D. J., Smoller, J. W., Stanaway, I. B., Wei, W. Q., Weng, C., & Ritchie, M. D. (2022). Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders. Nature communications, 13(1), Article 3428. https://doi.org/10.1038/s41467-022-30678-w

Zhang, X, Lucas, AM, Veturi, Y, Drivas, TG, Bone, WP, Verma, A, Chung, WK, Crosslin, D, Denny, JC, Hebbring, S, Jarvik, GP, Kullo, I, Larson, EB, Rasmussen-Torvik, LJ, Schaid, DJ, Smoller, JW, Stanaway, IB, Wei, WQ, Weng, C & Ritchie, MD 2022, 'Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders', Nature communications, vol. 13, no. 1, 3428. https://doi.org/10.1038/s41467-022-30678-w

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

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.",

author = "Xinyuan Zhang and Lucas, {Anastasia M.} and Yogasudha Veturi and Drivas, {Theodore G.} and Bone, {William P.} and Anurag Verma and Chung, {Wendy K.} and David Crosslin and Denny, {Joshua C.} and Scott Hebbring and Jarvik, {Gail P.} and Iftikhar Kullo and Larson, {Eric B.} and Rasmussen-Torvik, {Laura J.} and Schaid, {Daniel J.} and Smoller, {Jordan W.} and Stanaway, {Ian B.} and Wei, {Wei Qi} and Chunhua Weng and Ritchie, {Marylyn D.}",

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doi = "10.1038/s41467-022-30678-w",

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AU - Zhang, Xinyuan

AU - Lucas, Anastasia M.

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AU - Drivas, Theodore G.

AU - Bone, William P.

AU - Verma, Anurag

AU - Chung, Wendy K.

AU - Crosslin, David

AU - Denny, Joshua C.

AU - Hebbring, Scott

AU - Jarvik, Gail P.

AU - Kullo, Iftikhar

AU - Larson, Eric B.

AU - Rasmussen-Torvik, Laura J.

AU - Schaid, Daniel J.

AU - Smoller, Jordan W.

AU - Stanaway, Ian B.

AU - Wei, Wei Qi

AU - Weng, Chunhua

AU - Ritchie, Marylyn D.

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AB - 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.

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

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