title: Genetic influence on the progression of radiographic knee osteoarthritis: a longitudinal twin study.
abstract: OBJECTIVE
  Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study.
  
  
  METHODS
  Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation.
  
  
  RESULTS
  A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline.
  
  
  CONCLUSIONS
  Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.
authors.affiliation: Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK. guangju.zhai@kcl.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: D J
authors.initials: DJ
authors.lastname: Hart
authors.forename: B S
authors.initials: BS
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: MacGregor
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics*; D012307:Risk Factors