J Vasc Surg Venous Lymphat Disord. 2023 Aug 22:S2213-333X(23)00318-9. doi: 10.1016/j.jvsv.2023.08.007. Online ahead of print.
ABSTRACT
BACKGROUND: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by polygenes and multi-sites. 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.
OBJECTIVE: We aimed to construct a PRS model for the first episode of VTE in the Chinese population.
METHODS: (A) Single nucleotide polymorphisms (SNPs) associated with VTE in genome-wide association studies (GWAS), meta-analyses, and candidate gene studies were screened as variables in PRS. The logarithm of the odds ratio (OR) was used as the weight of the variables. (B) A training set with simulated data from 1,000 cases of VTE and 1,000 controls was created with different genotypes and frequencies. (C) We calculated the area under the receiver operating characteristic (ROC) curve (AUC) for evaluating 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 value of the PRS-53 model was 0.748 [95% confidence level (CI), 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 value for model optimization. The AUC value of the PRS-10 model containing 10 SNPs was 0.718 (95% CI, 0.696-0.740), with no statistical difference from the AUC value of the PRS-53 model containing 53 SNPs.
CONCLUSION: The PRS-10 and PRS-53 model showed similar prediction abilities and satisfactory discriminatory power, which 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.
PMID:37619711 | DOI:10.1016/j.jvsv.2023.08.007
