PREDICTIVE PERFORMANCE OF A POLYGENIC RISK SCORE FOR INCIDENT ISCHEMIC STROKE IN A HEALTHY OLDER POPULATION

Background and purpose Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. Methods We predicted risk of incident IS events in a population of 12 792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly). The PRS was calculated using 3.6 million genetic variants. Participants had no previous history of cardiovascular events, dementia, or persistent physical disability at enrollment. The primary outcome was IS over 5 years, with stroke subtypes as secondary outcomes. A multivariable model including conventional risk factors was applied and reevaluated after adding PRS. Area under the curve and net reclassification were evaluated. Results At baseline, mean population age was 75 years. In total, 173 incident IS events occurred over a median follow-up of 4.7 years. When PRS was added to the multivariable model as a continuous variable, it was independently associated with IS (hazard ratio, 1.41 [95% CI, 1.20-1.65] per SD of the PRS; P Conclusions PRS predicts incident IS in a healthy older population but only moderately improves prediction over conventional risk factors. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.