Int J Stroke. 2025 Nov 1:17474930251396062. doi: 10.1177/17474930251396062. Online ahead of print.
ABSTRACT
OBJECTIVE: To validate whether incorporating existing polygenic risk scores (PRSs) derived from East Asian or trans-ancestry populations into clinical risk equations improves stroke risk stratification in Chinese adults.
METHODS: Participants from the Chinese Multi-provincial Cohort study with genotyped data (n=2931) were included. Four well-established PRSs (i.e., PRS-GBMI, PRS-GIGA, PRS-ChinaPAR, PRS-MEGA) from either the predominantly Chinese or trans-ancestry populations were constructed and evaluated by assessing their associations with stroke and its subtypes. We tested the incremental predictive capability of the four PRSs on 10- and 20-year risk of stroke and its subtypes after adding PRSs to recalibrated China-PAR stroke risk equations, based on discrimination, calibration, and reclassification.
RESULTS: Over a median of 28.2 follow-up years, 340 stroke events were recorded. Higher PRSs were generally associated with a higher stroke risk, though only the highest quantile group of PRS-GIGA showed statistical significance (HR 1.79, 95% CI: 1.05-3.07). Adding PRS-GIGA to the recalibrated China-PAR stroke risk equations (i.e., the base model) yielded a moderate improvement in 20-year stroke risk, with 17.2% (95%CI: 3.8%-30.6%) more of participants correctly categorized into their corresponding risk groups. However, for ischemic stroke, adding PRS-GIGA, PRS-ChinaPAR, PRS-MEGA to the base model could correctly categorize 18.7%~23.8% more of participants into their corresponding 10-year risk groups and 27.8%~32.5% more of participants into their corresponding 20-year risk groups. Adding PRSs did not improve prediction for hemorrhagic stroke.
CONCLUSION: Adding existing PRSs, particularly PRS-GIGA, to clinical risk equations can improve all stroke and ischemic stroke risk stratification in Chinese adults.
PMID:41175054 | DOI:10.1177/17474930251396062
