{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:46:42Z","timestamp":1791600402961,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Polygenic risk scores (PRS) allow risk stratification using common single\u2010nucleotide 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 12,732 individuals from a population\u2010based cohort from the Rotterdam Study (n\u00a0=\u00a011,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n\u00a0=\u00a0908), and a high\u2010risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n\u00a0=\u00a0328), 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\u2010wide association study meta\u2010analysis. Standardized PRS (with Z transformation) were used in all analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20131.5) and 1.6 (95% CI 1.3\u20131.9) 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\u20131.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8\u20131.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4\u20133.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS\u2010based 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42246","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T04:24:27Z","timestamp":1653798267000},"page":"1488-1496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Risk Assessment for Hip and Knee Osteoarthritis Using Polygenic Risk Scores"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-8648","authenticated-orcid":false,"given":"Bahar","family":"Sedaghati\u2010Khayat","sequence":"first","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy G.","family":"Boer","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-6707","authenticated-orcid":false,"given":"Jos","family":"Runhaar","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita M. A.","family":"Bierma\u2010Zeinstra","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Broer","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-659X","authenticated-orcid":false,"given":"Eleftheria","family":"Zeggini","sequence":"additional","affiliation":[{"name":"Institute of Translational Genomics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany, and Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 G.","family":"Uitterlinden","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen G. 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