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@article{Yuan:2021:10.1161/JAHA.120.019644,
author = {Yuan, S and Burgess, S and Laffan, M and Mason, AM and Dichgans, M and Gill, D and Larsson, SC},
doi = {10.1161/JAHA.120.019644},
journal = {Journal of the American Heart Association},
pages = {1--20},
title = {Genetically proxied inhibition of coagulation factors and risk of cardiovascular disease: a mendelian randomization study},
url = {http://dx.doi.org/10.1161/JAHA.120.019644},
volume = {10},
year = {2021}
}

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TY  - JOUR
AB  - BackgroundWe conducted Mendelian randomization analyses investigating the linear associations of genetically proxied inhibition of different coagulation factors with risk of common cardiovascular diseases.Methods and ResultsGenetic instruments proxying coagulation factor inhibition were identified from genomewide association studies for activated partial thromboplastin time and prothrombin time in BioBank Japan (up to 58 110 participants). Instruments were identified for 9 coagulation factors (fibrinogen alpha, beta, and gamma chain; and factors II, V, VII, X, XI, and XII). Age and sexadjusted estimates for associations of the instruments with the outcomes were derived from UK Biobank and the FinnGen, CARDIoGRAMplusC4D (Coronary Artery Disease Genomewide Replication and Metaanalysis), and MEGASTROKE consortia with numbers of incident and prevalent cases of 820 to 60 810. Genetically proxied inhibition of fibrinogen alpha, beta, and gamma chain, factor II, and factor XI were associated with reduced risk of venous thromboembolism (P<0.001). With the exception of fibrinogen beta and factor II, inhibition of these factors was also associated with reduced risk of any ischemic stroke and cardioembolic stroke (P≤0.002). Genetically proxied inhibition of fibrinogen beta and gamma were associated with reduced largeartery stroke risk (P=0.001). There were suggestive protective associations of genetically proxied inhibition of factors V, VII, and X with ischemic stroke (P<0.05), and suggestive adverse associations of genetically proxied inhibition of factors II and XII with subarachnoid hemorrhage.ConclusionsThis study supports targeting fibrinogen and factor XI for reducing venous thromboembolism and ischemic stroke risk, and showed suggestive evidence that inhibition of factors V, VII, and X might reduce ischemic stroke risk.
AU  - Yuan,S
AU  - Burgess,S
AU  - Laffan,M
AU  - Mason,AM
AU  - Dichgans,M
AU  - Gill,D
AU  - Larsson,SC
DO  - 10.1161/JAHA.120.019644
EP  - 20
PY  - 2021///
SN  - 2047-9980
SP  - 1
TI  - Genetically proxied inhibition of coagulation factors and risk of cardiovascular disease: a mendelian randomization study
T2  - Journal of the American Heart Association
UR  - http://dx.doi.org/10.1161/JAHA.120.019644
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000641743900024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.ahajournals.org/doi/10.1161/JAHA.120.019644
UR  - http://hdl.handle.net/10044/1/94512
VL  - 10
ER  -

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