Hollis B, Chatzigeorgiou C, Southam L, Hatzikotoulas K, Kluzek S, Williams A, Zeggini E, Jostins-Dean L, Watt F E
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.
Institute of Translational Genomics, Helmholtz, Munich, Germany.
Osteoarthritis Cartilage. 2023 Oct;31(10):1377-1387. doi: 10.1016/j.joca.2023.05.012. Epub 2023 May 27.
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).
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.
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. 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]).
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.
急性膝关节损伤与创伤后骨关节炎（PTOA）相关。与特发性骨关节炎（iOA）相比，关于PTOA全基因组关联的了解甚少。我们的目的是描述英国生物银行（UKB）中膝关节损伤后膝骨关节炎的发展及其遗传关联。
从502,409名UKB参与者的电子健康记录和自我报告数据中识别出年龄≤50岁的具有临床意义的结构性膝关节损伤。使用Cox比例风险模型比较受伤病例和年龄/性别匹配的未受伤对照中首次出现膝关节骨关节炎（OA）编码的时间。一项OA全基因组关联研究（GWAS）旨在寻找损伤后6个月至20年PTOA风险变异的证据。寻找两个iOA多基因风险评分（PRS）关联的证据。
在4233例膝关节损伤病例中，1896例（44.8%）为女性（受伤时平均年龄34.1岁[标准差10.4]）。在中位数为30.2（四分位间距19.5 - 45.4）年的时间里，1096例（25.9%）受伤病例发展为膝骨关节炎。受伤后膝骨关节炎的总体风险比（HR）为1.81（1.70,1.93），P = 8.9×10。女性性别和受伤时年龄增加与受伤后膝骨关节炎相关（HR分别为1.15[1.02,1.30]；1.07[1.07,1.07]）。骨关节炎风险在受伤后的前5年最高（HR 3.26[2.67,3.98]），持续40年。在纳入OA GWAS的3074例膝关节损伤病例中，没有变异达到全基因组显著性。iOA PRS与OA发生时间无关（HR 0.43[0.02,8.41]）。
在UKB中，受伤时年龄增加和女性性别似乎与PTOA的未来发展相关，其风险在受伤后的5年中最大。进一步开展国际合作进行功效更强的荟萃分析将明确阐明PTOA和iOA的遗传异同。
