Risk Assessment for Hip and Knee Osteoarthritis Using Polygenic Risk Scores

Bahar Sedaghati-Khayat, Cindy G. Boer, Jos Runhaar, Sita M.A. Bierma-Zeinstra, Linda Broer, M. Arfan Ikram, Eleftheria Zeggini, André G. Uitterlinden, Jeroen G.J. van Rooij, Joyce B.J. van Meurs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Objective: Polygenic risk scores (PRS) allow risk stratification using common single-nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS. Methods: We analyzed 12,732 individuals from a population-based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high-risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome-wide association study meta-analysis. Standardized PRS (with Z transformation) were used in all analyses. Results: We found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1–1.5) and 1.6 (95% CI 1.3–1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1–1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8–1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4–3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution. Conclusion: Our findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS-based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.

Original languageEnglish
Pages (from-to)1488-1496
Number of pages9
JournalArthritis and Rheumatology
Issue number9
Publication statusPublished - Sep 2022

Bibliographical note

The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating GPs and pharmacists. The authors are thankful to the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands for the generation and management of genotype data for the Rotterdam Study (RS‐I, RS‐II, RS‐III), CHECK, and PROOF cohorts.

Funding Information:
Supported by GOALL project. The GOALL project was funded by the internal Koers23 program from the Erasmus Medical Center (project no. 109433). The PROOF study was funded by The Netherlands Organisation for Health Research and Development (ZonMw) and a FP7 Programm Grant (D‐BOARD) by the European Committee. The CHECK study was supported by The Dutch Arthritis Society (ReumaNederland).

Publisher Copyright:
© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.


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