The genetic contribution to severe post-traumatic osteoarthritis
- Ana M Valdes1,2,
- Sally A Doherty1,
- Kenneth R Muir3,4,
- Margaret Wheeler1,
- Rose A Maciewicz5,
- Weiya Zhang1,
- Michael Doherty1
- 1Academic Rheumatology, Nottingham City Hospital, Nottingham, UK
- 2Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas’ Hospital, London, UK
- 3Health Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK
- 4Institute of Population Health, University of Manchester, Manchester, UK
- 5Respiratory & Inflammation Research Area, AstraZeneca, Charnwood R&D, Loughborough, Leicestershire, UK
- Correspondence to Dr Ana M Valdes, Department of Twin Research & Genetic Epidemiology, Kings College London, St Thomas Hospital campus, London SE1 7EH, UK;
- Received 24 August 2012
- Revised 6 December 2012
- Accepted 29 December 2012
- Published Online First 26 January 2013
Objective To compare the combined role of genetic variants loci associated with risk of knee or hip osteoarthritis (OA) in post-traumatic (PT) and non-traumatic (NT) cases of clinically severe OA leading to total joint replacement.
Methods A total of 1590 controls, 2168 total knee replacement (TKR) cases (33.2% PT) and 1567 total hip replacement (THR) cases (8.7% PT) from 2 UK cohorts were genotyped for 12 variants previously reported to be reproducibly associated with risk of knee or hip OA. A genetic risk score was generated and the association with PT and NT TKR and THR was assessed adjusting for covariates.
Results For THR, each additional genetic risk variant conferred lower risk among PT cases (OR=1.07, 95% CI 0.96 to 1.19; p=0.24) than NT cases (OR 1.11, 95% CI 1.06 to 1.17; p=1.55×10−5). In contrast, for TKR, each risk variant conferred slightly higher risk among PT cases (OR 1.12, 95% CI 1.07 to 1.19; p=1.82×10−5) than among NT cases (OR 1.08, 95% CI 1.03 to 1.1; p=0.00063).
Conclusions Based on the variants reported to date PT TKR cases have at least as high a genetic contribution as NT cases.
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