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Sedaghati-Khayat, B.* ; Boer, C.G.* ; Runhaar, J.* ; Bierma-Zeinstra, S.M.A.* ; Broer, L.* ; Ikram, M.A.* ; Zeggini, E. ; Uitterlinden, A.G.* ; van Rooij, J.G.J.* ; van Meurs, J.B.J.*

Risk assessment for hip and knee osteoarthritis using polygenic risk scores.

Arthritis Rheum. 74, 1488-1496 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
OBJECTIVES: Polygenic risk scores (PRS) allow risk-stratification using common SNPs, and clinical applications are currently explored for several diseases. This study used PRS to assess the risk for hip- and knee-Osteoarthritis (OA). METHODS: We analyzed 12,732 individuals from a population-based cohort of the Rotterdam Study (RS;n=11,496), a clinical cohort (CHECK;n=908), and a high-risk cohort of overweight women (PROOF;n=328), for the association of the PRSs with prevalence/incidence of radiographic-OA, of clinical-OA, and of total hip- or knee-replacement (THR/TKR). The hip-PRS and knee-PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent GWAS meta-analysis. Standardized PRSs (Z-transformation) were used in all analyses. RESULTS: We found a stronger association of the PRSs for clinically-defined OA compared to radiographic-OA phenotypes. 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 (CI) [1.1-1.5]) and 1.6[1.3-1.9] for incident TKR in RS. The knee-PRS was associated with incident clinical-knee-OA in CHECK 1.3[1.1-1.5], but not for PROOF 1.2[0.8-1.7]. The OR for OA increased gradually across the PRSs distribution, up to 2.1[1.4-3.2] for individuals with the 10% highest PRS compared to the middle 50% of the PRSs distribution. CONCLUSIONS: The findings validated the association of PRSs 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 PRSs utility is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings. This article is protected by copyright. All rights reserved.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0004-3591
e-ISSN 1529-0131
Zeitschrift Arthritis & Rheumatology
Quellenangaben Band: 74, Heft: 9, Seiten: 1488-1496 Artikelnummer: , Supplement: ,
Verlag Wiley
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)