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Thromb Haemost 2021; 121(09): 1169-1180
DOI: 10.1055/s-0041-1723988
Coagulation and Fibrinolysis

Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism

Marisol Herrera-Rivero‡   *
1   Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany
,
Monika Stoll   *
1   Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany
2   Department of Biochemistry, Genetic Epidemiology and Statistical Genetics, Maastricht University, Maastricht, The Netherlands
,
Jana-Charlotte Hegenbarth
1   Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany
,
Frank Rühle
1   Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany
,
Verena Limperger 
3   Institute for Clinical Chemistry and Coagulation Center, University Hospital Schleswig Holstein, Kiel/Lübeck, Germany
,
Ralf Junker
3   Institute for Clinical Chemistry and Coagulation Center, University Hospital Schleswig Holstein, Kiel/Lübeck, Germany
,
André Franke
4   Institute for Clinical Molecular Biology, University Hospital Schleswig Holstein, Kiel, Germany
,
Per Hoffmann
5   Life and Brain Research Centre, University of Bonn, Bonn, Germany
,
Maria Shneyder
3   Institute for Clinical Chemistry and Coagulation Center, University Hospital Schleswig Holstein, Kiel/Lübeck, Germany
,
Michael Stach
6   IT Service Centre, University Hospital Münster, Münster, Germany
,
Ulrike Nowak-Göttl
3   Institute for Clinical Chemistry and Coagulation Center, University Hospital Schleswig Holstein, Kiel/Lübeck, Germany
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Abstract

Previous genome-wide association studies (GWASs) have established several susceptibility genes for venous thromboembolism (VTE) and suggested many others. However, a large proportion of the genetic variance in VTE remains unexplained. Here, we report genome-wide single- and multimarker as well as gene-level associations with VTE in 964 cases and 899 healthy controls of European ancestry. We report 19 loci at the genome-wide level of association (p ≤ 5 × 10−8). Our results add to the strong support for the association of genetic variants in F5, NME7, ABO, and FGA with VTE, and identify several loci that have not been previously associated with VTE. Altogether, our novel findings suggest that 20 susceptibility genes for VTE were newly discovered by our study. These genes may impact the production and prothrombotic functions of platelets, endothelial cells, and white and red blood cells. Moreover, the majority of these genes have been previously associated with cardiovascular diseases and/or risk factors for VTE. Future studies are warranted to validate our findings and to investigate the shared genetic architecture with susceptibility factors for other cardiovascular diseases impacting VTE risk.

Keywords

genome wide association studies - venous thromboembolism - genetic risk - susceptibility loci

Authors' Contributions

M.H.-R. and M.Sto. contributed equally to this work. M.Sto. and U.N.-G. conceived and designed the study, and made critical revisions to the manuscript. M.H.-R. performed all analyses and prepared the manuscript. J.-C.H. and F.R. processed the data and performed preliminary analyses. V.L., R.J., M.Sh., and U.N.-G. were responsible for patient ascertainment. A.F. and P.H. performed the genotyping of the patient and control cohorts. M.Sta. programmed and maintains the database for patient data. All authors approved the final version of the manuscript.


* These authors contributed equally.


Supplementary Material



Publication History

Received: 01 October 2020

Accepted: 28 December 2020

Article published online:
16 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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