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Objective. Prevention of osteoarthritis (OA) remains important, as there are no disease-modifying treatments. A personalized approach has the potential to better target prevention strategies. In the present study, we used recently identified genetic risk variants from genome-wide association analysis for advanced OA to calculate polygenic risk scores (PRS) for knee and hip OA and assessed PRS performance in an independent population of older communitydwelling adults.Methods. PRS were calculated in 12,093 individuals of European genetic descent ages ≥70 years who were enrolled in the Aspirin in Reducing Events in the Elderly trial. The outcome measure was knee and hip replacement (hospitalizations during the trial and self-reported joint replacements before enrollment). PRS were considered as continuous (per SD) and categorical (low risk [0-20%], medium risk [21-80%], high risk [81-100%]) variables. Logistic regression was used to examine associations between PRS and risk of joint replacement, adjusted for age, sex, body mass index, and socioeconomic status.Results. Among the participants, 1,422 (11.8%) had knee replacements and 1,297 (10.7%) had hip replacements. PRS (per SD) were associated with a risk of knee replacement (odds ratio [OR] 1.13 [95% confidence interval (95% CI) 1.07-1.20]) and hip replacement (OR 1.23 [95% CI 1.16-1.30]). Participants with high PRS had an increased risk of knee replacement ) and hip replacement ), compared to those with low PRS. Associations were stronger for PRS and hip replacement risk in women than in men. Associations were similar in sensitivity analyses that examined joint replacements before and during the trial separately.Conclusion. PRS have the potential to improve prevention of severe knee and hip OA by providing a personalized approach and identifying individuals who may benefit from early intervention.

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