Genetic associations of protein-coding variants in venous thromboembolism

Xiao-Yu He, Bang-Sheng Wu, Liu Yang, Yu Guo, Yue-Ting Deng, Ze-Yu Li, Chen-Jie Fei, Wei-Shi Liu, Yi-Jun Ge, Jujiao Kang, Jianfeng Feng, Wei Cheng (), Qiang Dong () and Jin-Tai Yu ()
Additional contact information
Xiao-Yu He: Fudan University
Bang-Sheng Wu: Fudan University
Liu Yang: Fudan University
Yu Guo: Fudan University
Yue-Ting Deng: Fudan University
Ze-Yu Li: Fudan University
Chen-Jie Fei: Fudan University
Wei-Shi Liu: Fudan University
Yi-Jun Ge: Fudan University
Jujiao Kang: Fudan University
Jianfeng Feng: Fudan University
Wei Cheng: Fudan University
Qiang Dong: Fudan University
Jin-Tai Yu: Fudan University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47178-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47178-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47178-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().