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Multi-ancestry polygenic risk scores for venous thromboembolism.

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- (PRSCSXEUR: AUC=0.61 (0.60, 0.61), PRSCSX_combinedEUR: AUC=0.61 (0.60, 0.62)) and African-ancestry test samples (PRSCSXAFR: AUC=0.58 (0.57, 0.6), PRSCSX_combined AFR: 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.

SUBMITTER: Jee YH 

PROVIDER: S-EPMC10802635 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Multi-ancestry polygenic risk scores for venous thromboembolism.

Jee Yon Ho YH   Thibord Florian F   Dominguez Alicia A   Sept Corriene C   Boulier Kristin K   Venkateswaran Vidhya V   Ding Yi Y   Cherlin Tess T   Verma Shefali Setia SS   Faro Valeria Lo VL   Bartz Traci M TM   Boland Anne A   Brody Jennifer A JA   Deleuze Jean-Francois JF   Emmerich Joseph J   Germain Marine M   Johnson Andrew D AD   Kooperberg Charles C   Morange Pierre-Emmanuel PE   Pankratz Nathan N   Psaty Bruce M BM   Reiner Alexander P AP   Smadja David M DM   Sitlani Colleen M CM   Suchon Pierre P   Tang Weihong W   Trégouët David-Alexandre DA   Zöllner Sebastian S   Pasaniuc Bogdan B   Damrauer Scott M SM   Sanna Serena S   Snieder Harold H   Kabrhel Christopher C   Smith Nicholas L NL   Kraft Peter P  

medRxiv : the preprint server for health sciences 20240110

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 en  ...[more]