Construction and optimization of a polygenic risk model for venous thromboembolism in the Chinese population.

Background: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by polygenes and multisites. The polygenic risk score (PRS) has been widely used because any single genetic biomarker failed to accurately predict the genetic risk of VTE. However, no polygenic risk model has been proposed for VTE in the Chinese population. Thus, we aimed to construct a PRS model for the first episode of VTE in the Chinese population.

Methods: First, single nucleotide polymorphisms (SNPs) associated with VTE in genome-wide association studies, meta-analyses, and candidate gene studies were screened as variables for the PRS. The logarithm of the odds ratio was used to weight the variables. Second, a training set with simulated data from 1000 cases of VTE and 1000 controls was created with different genotypes and frequencies. Finally, we calculated the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory ability of the PRS model.

Results: We screened 53 SNPs potentially associated with the first episode of VTE in the Chinese population. The AUC of the PRS-53 model (containing 53 SNPs) was 0.748 (95% confidence interval, 0.727-0.770) in the training set. From the largest weight to the smallest weight, SNPs were incrementally added to the model to calculate the AUC for model optimization. The AUC of the PRS-10 model (containing 10 SNPs) was 0.718 (95% confidence interval, 0.696-0.740), with no statistically significant difference from the AUC for the PRS-53 model.

Conclusions: The PRS-10 and PRS-53 models showed similar predictive abilities and satisfactory discriminatory power and can be used to predict the genetic risk of the first episode of VTE in the Chinese population. The simplified PRS-10 model is more efficient in clinical practice.