Development of a MassARRAY Genotyping Platform and Its Clinical Application for Venous Thromboembolism Risk...

Background: Venous thromboembolism (VTE) is a multifactorial disorder influenced by both genetic and environmental factors, with substantial variability in susceptibility across populations. Data on VTE-associated genetic variants in Asian populations, including Thais, remain limited. To address this, we developed a 39-single-nucleotide polymorphism (SNP) genotyping panel using the MassARRAY platform and evaluated its association with VTE in a Thai cohort. Methods: A total of 209 individuals, comprising 122 patients with objectively confirmed VTE and 87 age- and sex-matched healthy controls, were genotyped. Allele frequencies were compared, and associations with VTE were assessed. Results: Seven SNPs demonstrated significant associations: five risk alleles (PROC rs146922325, ABO rs8176743, FGG rs2066865, F11 rs4253417, and HIVEP1 rs169713) and two protective alleles (F5 rs4524 and TGFB2 rs57615042). To examine cumulative effects, a polygenic risk score (PRS) integrating genetic and clinical factors was constructed. Higher PRS was significantly associated with recurrence, particularly among patients with unprovoked VTE, conferring more than a threefold increase in recurrence risk (HR = 3.53, 95% CI: 1.04-10.2, p = 0.043). These findings provide the first systematic evidence of population-specific genetic risk factors for VTE in Thais and highlight the clinical potential of PRS for recurrence prediction. Conclusions: The MassARRAY-based panel offers a cost-effective, high-throughput strategy for simultaneous SNP detection, supporting scalable genomic studies and personalized risk stratification. Our results contribute to understanding the genetic architecture of VTE and highlight the value of incorporating non-European populations into genetic studies to advance precision medicine.