Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. - Université de Bretagne Occidentale Access content directly
Journal Articles American Journal of Human Genetics Year : 2015

Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism.

1 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
2 Brigham and Women's Hospital [Boston]
3 Department of Thrombosis and Haemostasis
4 UMN - University of Minnesota [Twin Cities]
5 PGESG - BOSTON - Program in Genetic Epidemiology and Statistical Genetics
6 MC - Mayo Clinic
7 ELEVM - LEIDEN - Einthoven Laboratory for Experimental Vascular Medicine
8 Department of Epidemiology
9 NORT - Nutrition, obésité et risque thrombotique
10 Laboratoire d'hématologie
11 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
12 HEGP - Hôpital Européen Georges Pompidou [APHP]
13 IThEM - U1140 - Innovations thérapeutiques en hémostase
14 CIC - Brest - Centre d'Investigation Clinique
15 MR - Service d'angiologie et d'hémostase
16 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
17 Department of Genetics and Genomic Sciences
18 NIHR Leicester Cardiovascular Biomedical Research Unit
19 Department of Cardiovascular Sciences [Leicester]
20 DPG - COPENHAGEN - Department of PharmacoGenetics
21 Department of Medical Statistics and Bioinformatics
22 HMS - Harvard Medical School [Boston]
23 University of Washington [Seattle]
24 Section Molecular Epidemiology, Leiden University Medical Center (LUMC)
25 Division of epidemiology
26 CNG - Centre National de Génotypage
27 Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders
28 William Harvey Research Institute, Barts and the London Medical School
29 Epidémiologie et Biostatistique [Bordeaux]
30 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
31 LA Biomed Res Institute - Los Angeles Biomedical Research Institute and Department of Pediatrics
32 Department of medicine [Stockholm]
33 Atherosclerosis Research Unit
34 Group Health Research Institute, Group Health Cooperative
35 Université de Lille
36 Institut Pasteur de Lille
37 Leicester NIHR Biomedical Research Unit in Cardiovascular Disease
38 Biostat - MINNEAPOLIS - Division of Biostatistics
39 Department of Emergency Medicine
40 Division of Cardiovascular Diseases
41 Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development
42 Fibrinolyse et Pathologie Vasculaire
Mariza de Andrade
  • Function : Author
Ke Hao
Jean-François Deleuze
  • Function : Author
  • PersonId : 1015006

Abstract

Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10(-16)) and 1.21 (p = 2.75 × 10(-15)), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology.

Dates and versions

hal-01259946 , version 1 (21-01-2016)

Identifiers

Cite

Marine Germain, Daniel I Chasman, Hugoline de Haan, Weihong Tang, Sara Lindström, et al.. Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism.. American Journal of Human Genetics, 2015, 96 (4), pp.532-42. ⟨10.1016/j.ajhg.2015.01.019⟩. ⟨hal-01259946⟩
292 View
0 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More