title: The association of body mass index and osteoarthritis of the knee joint: an examination of genetic and environmental influences.
abstract: OBJECTIVE
  To examine the genetic and environmental influences on the known association between body mass index (BMI) and knee osteoarthritis (OA), using adult twin data.
  
  
  METHODS
  Bilateral knee radiographs were obtained from 785 pairs of healthy female twins (mean age 54.5 +/- 7.8 years) from the St. Thomas' Hospital Adult Twin Registry (261 monozygotic [MZ] and 524 dizygotic [DZ] twin pairs). Tibiofemoral knee OA was graded according to the Kellgren and Lawrence (K/L) scoring system on an ordinal scale of 0-4. Presence of knee OA was defined as a K/L grade of > or =2 on either side of the knee joint. Body weight and height were measured and the subjects were stratified into quartiles of BMI. Cross-trait cross-twin association of BMI and knee OA was assessed by logistic regression, to assess whether genetic or environmental influences explain the BMI-knee OA link. The genetic (heritability) and environmental contributions to each of the measures were estimated using path modeling.
  
  
  RESULTS
  A strong association was found between high BMI and the presence of knee OA (odds ratio 3.90 for highest versus lowest quartile of BMI; P = 0.0001). The heritability of knee OA was 50.4% (95% confidence interval [95% CI] 34-62%) and that of BMI was 55.7% (95% CI 35-72%). However, cross-trait cross-twin associations were not significantly different from unity in either the MZ or DZ twin pairs, indicating that shared genetic influences were unlikely to explain the association. Path modeling showed that the model containing additive genetic factors, common environmental factors, and unique environmental factors had the best fit to the data overall. The shared genetic path between BMI and knee OA could be dropped without deterioration in the fit of the model.
  
  
  CONCLUSIONS
  The strong association between high BMI and knee OA is not likely to be mediated by shared genetic factors. The results imply that environmental modification of BMI can influence knee OA.
authors.affiliation: Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London, UK. manek.nisha@mayo.edu
authors.forename: Nisha J
authors.initials: NJ
authors.lastname: Manek
authors.forename: Deborah
authors.initials: D
authors.lastname: Hart
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: MacGregor
mesh_terms: D015992:Body Mass Index; D004200:Diseases in Twins / Q000453:epidemiology; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology*; D011859:Radiography; D012042:Registries; D012307:Risk Factors; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D006113:United Kingdom / Q000453:epidemiology