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

Content Provider	Scilit
Author	Herrera-Rivero, Marisol Stoll, Monika Hegenbarth, Jana-Charlotte Rühle, Frank Limperger, Verena Junker, Ralf Franke, André Hoffmann, Per Shneyder, Maria Stach, Michael Nowak-Göttl, Ulrike
Copyright Year	2021
Description	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. 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. Received: 01 October 2020 Accepted: 28 December 2020 Publication Date: 16 February 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
Related Links	http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0041-1723988.pdf
Ending Page	1180
Page Count	12
Starting Page	1169
ISSN	2567689X
DOI	10.1055/s-0041-1723988
Journal	Thrombosis and Haemostasis
Issue Number	09
Volume Number	121
Language	English
Publisher	Georg Thieme Verlag KG
Publisher Date	2021-02-16
Access Restriction	Open
Subject Keyword	Journal: Thrombosis and Haemostasis Peripheral Vascular Disease Genome Wide Association Studies Venous Thromboembolism Genetic Risk Susceptibility Loci
Content Type	Text
Resource Type	Article
Subject	Hematology