Meta-analysis of 65,734 Individuals Identifies TSPAN15 and SLC44A2 as Two Susceptibility Loci for Venous Thromboembolism

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