Imperial College London
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ProfessorAbbasDehghan

Faculty of Medicine, School of Public Health

Professor in Molecular Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Maners:2020:10.1182/blood.2019004781,
author = {Maners, J and Gill, D and Pankratz, N and Laffan, MA and Wolberg, AS and de, Maat MPM and Ligthart, S and Tang, W and Ward-Caviness, CK and Fomage, M and Debette, S and Dichgans, M and McKnight, B and Boerwinkle, E and Smith, NL and Morrison, AC and Dehghan, A and de, Vries PS},
doi = {10.1182/blood.2019004781},
journal = {Blood},
pages = {3062--3069},
title = {A Mendelian randomization of γ′ and total fibrinogen levels in relation to venous thromboembolism and ischemic stroke},
url = {http://dx.doi.org/10.1182/blood.2019004781},
volume = {136},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ′) fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied 2-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ′ fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies. Genetic instruments for γ′ fibrinogen and total fibrinogen were selected, and the inverse-variance weighted MR approach was used to estimate causal effects in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger, weighted median MR, and weighted mode MR. The main inverse-variance weighted MR estimates based on a combination of 16 genetic instruments for γ′ fibrinogen and 75 genetic instruments for total fibrinogen indicated a protective effect of higher γ′ fibrinogen and higher total fibrinogen on VTE risk. There was also a protective effect of higher γ′ fibrinogen levels on cardioembolic and large artery stroke risk. Effect estimates were consistent across sensitivity analyses. Our results provide evidence to support effects of genetically determined γ′ fibrinogen on VTE and ischemic stroke risk. Further research is needed to explore mechanisms underlying these effects and their clinical applications.
AU  - Maners,J
AU  - Gill,D
AU  - Pankratz,N
AU  - Laffan,MA
AU  - Wolberg,AS
AU  - de,Maat MPM
AU  - Ligthart,S
AU  - Tang,W
AU  - Ward-Caviness,CK
AU  - Fomage,M
AU  - Debette,S
AU  - Dichgans,M
AU  - McKnight,B
AU  - Boerwinkle,E
AU  - Smith,NL
AU  - Morrison,AC
AU  - Dehghan,A
AU  - de,Vries PS
DO  - 10.1182/blood.2019004781
EP  - 3069
PY  - 2020///
SN  - 0006-4971
SP  - 3062
TI  - A Mendelian randomization of γ′ and total fibrinogen levels in relation to venous thromboembolism and ischemic stroke
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood.2019004781
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000603450500015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://ashpublications.org/blood/article-abstract/136/26/3062/461598/A-Mendelian-randomization-of-and-total-fibrinogen?redirectedFrom=fulltext
UR  - http://hdl.handle.net/10044/1/88304
VL  - 136
ER  -
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