Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank.

Autor: Hollis B; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom., Chatzigeorgiou C; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom., Southam L; Institute of Translational Genomics, Helmholtz, Munich, Germany., Hatzikotoulas K; Institute of Translational Genomics, Helmholtz, Munich, Germany., Kluzek S; Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, University of Nottingham, Nottingham, United Kingdom., Williams A; Fortius Clinic, London, United Kingdom., Zeggini E; Institute of Translational Genomics, Helmholtz, Munich, Germany., Jostins-Dean L; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom., Watt FE; Department of Immunology and Inflammation, Imperial College London, London, United Kingdom; Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom. Electronic address: f.watt@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Oct; Vol. 31 (10), pp. 1377-1387. Date of Electronic Publication: 2023 May 27.
DOI: 10.1016/j.joca.2023.05.012
Abstrakt: Objective: Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after a knee injury and its genetic associations in UK Biobank (UKB).
Design: Clinically significant structural knee injuries in those ≤50 years were identified from electronic health records and self-reported data in 502,409 UKB participants. Time-to-first knee osteoarthritis (OA) code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months to 20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought.
Results: Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD 10.4]). Over a median of 30.2 (IQR 19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81 (1.70,1.93), P = 8.9 × 10 -74 . Female sex and increasing age at injury were associated with knee OA following injury (HR 1.15 [1.02,1.30];1.07 [1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR 3.26 [2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43 [0.02,8.41]).
Conclusions: Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA.
Competing Interests: Declaration of Competing Interest FW has received personal consulting fees in 2020 from Pfizer for an unrelated compound. She is an associate editor for Osteoarthritis and Cartilage. Her institution received funding from Versus Arthritis for her role as lead of a Versus Arthritis Research Advisory Group. No other authors declare a conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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