title: Genetic predisposition to the presence and 5-year clinical progression of hip osteoarthritis.
abstract: OBJECTIVE
  Genetic factors are important in the aetiology of hip osteoarthritis (OA), but studies are limited by cross-sectional design and poor association with clinically important disease. Identifying cohorts with progressive OA will facilitate development of OA biomarkers. Using a middle-aged cohort with genetic predisposition to hip OA and a control group, we compared the prevalence of clinical and radiographic hip OA and incidence of progression over 5 years.
  
  
  METHODS
  123 individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) ('sibkids') were compared with 80 (mean age 54 years) controls. The prevalence of radiographic OA [scored according to Kellgren & Lawrence (K&L)], clinical features, and incidence of clinical progression over a 5-year period were compared. A multivariate logistic regression model was used to adjust for confounders.
  
  
  RESULTS
  Sibkids had odds ratios (ORs) of 2.7 [95% confidence interval (CI) 1.1-6.3, P = 0.02] for hip OA (K&L grade ≥2), 3.4 (1.4-8.4, P = 0.008) for clinical signs, and 2.1 (0.8-5.8, P = 0.14) for signs and symptoms. Over 5 years, sibkids had ORs of 4.7 (1.7-13.2, P = 0.003) for the development of signs, and 3.2 (1.0-10.3, P = 0.047) for the development of signs and symptoms.
  
  
  CONCLUSIONS
  Compared to a control group and after adjustment for confounders, individuals with genetic predisposition to end-stage hip OA have higher prevalence of OA, clinical features, and progression. In addition to structural degeneration, the inherited risk may include predisposition to pain. Genetically-loaded cohorts are useful to develop hip OA biomarkers, as they develop progressive disease at a young age.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom. Electronic address: Tom.Pollard@ndorms.ox.ac.uk.
authors.forename: T C B
authors.initials: TCB
authors.lastname: Pollard
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: R N
authors.initials: RN
authors.lastname: Batra
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Judge
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Watkins
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: E G
authors.initials: EG
authors.lastname: McNally
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: H S
authors.initials: HS
authors.lastname: Gill
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: N K
authors.initials: NK
authors.lastname: Arden
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and the NIHR Biomedical Research Unit, University of Oxford, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Carr
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D011859:Radiography