AI Article Synopsis

  • Venous thromboembolism (VTE) significantly affects health outcomes and shows disparities in incidence between Black and White Americans, necessitating improved risk assessment methods.* -
  • Polygenic risk scores (PRSs) derived from diverse ancestry data performed better than traditional PRSs, indicating their potential for accurately identifying high-risk individuals for VTE in both European and African ancestries.* -
  • The study found that using multi-ancestry PRSs could enhance risk stratification, with individuals in the highest risk category having a substantially increased likelihood of VTE, suggesting a path towards personalized treatment approaches.*

Article Abstract

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium GWAS meta-analyses of European- (71,771 cases and 1,059,740 controls) and African-ancestry samples (7,482 cases and 129,975 controls). We used LDpred2 and PRSCSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6,261 cases and 88,238 controls) and African-ancestry sample (1,385 cases and 12,569 controls). Multi-ancestry PRSs with weights tuned in European- and African-ancestry samples, respectively, outperformed ancestry-specific PRSs in European- (PRSCSX: AUC=0.61 (0.60, 0.61), PRSCSX_combined: AUC=0.61 (0.60, 0.62)) and African-ancestry test samples (PRSCSX: AUC=0.58 (0.57, 0.6), PRSCSX_combined : AUC=0.59 (0.57, 0.60)). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS may be used to identify individuals at highest risk for VTE and provide guidance for the most effective treatment strategy across diverse populations.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802635PMC
http://dx.doi.org/10.1101/2024.01.09.24300914DOI Listing

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