GP6 polymorphisms and venous thromboembolism: a Chinese case-control study with cross-population assessment

BACKGROUND: While genome-wide association studies having implicated the GP6 rs1613662 polymorphism as a risk factor for venous thrombosis, subsequent studies have reported inconsistent findings regarding this association. OBJECTIVES: Here, we performed a case-control study in a Chinese cohort to evaluate the association between rs1613662 and venous thromboembolism (VTE) risk. We further conducted‌ a comprehensive cross-population assessment by integrating multi-ethnic data to assess this association. METHODS: We recruited 225 patients with VTE and 203 healthy controls for the Chinese case-control study, with rs1613662 genotyped using the Sequenom assay. Additionally, we systematically integrated genotyping data from nine cohorts (with a total of 5,669 VTE cases and 8,976 controls) for the cross-population analysis. RESULTS: Analysis of the Chinese cohort revealed no statistically significant association between rs1613662 and VTE susceptibility. However, the multi-ethnic meta-analysis revealed significant VTE risk associations for rs1613662 in both the additive (odds ratio [OR] = 1.14, 95% confidence interval [CI]:1.07-1.22, P = 0.00014) and dominant models (OR = 1.16, 95% CI:1.07-1.25, P = 0.00019), but not in the recessive model (OR = 1.22, 95% CI:0.96-1.52, P = 0.082). Sensitivity analysis via the sequential exclusion of individual studies demonstrated remarkable stability. CONCLUSIONS: Our findings demonstrate that rs1613662 is associated with a modest but statistically significant increase in VTE susceptibility on average, with heterogeneous effect sizes across different populations. The observed ethnic heterogeneity suggests the necessity of additional investigation into population-specific genetic architectures. Integrated polygenic risk scores could be used to optimize risk stratification and develop preventive strategies against VTE.