Nature vs nurture in knee osteoarthritis - the importance of age, sex and body mass index

Osteoarthritis Cartilage. 2019 Apr;27(4):586-592. doi: 10.1016/j.joca.2018.12.018. Epub 2019 Jan 8.


Objective: (1) To estimate the life-time genetic contribution for knee osteoarthritis (OA) surgery and (2) to explore any differences in the genetic contribution across age, sex and body mass index (BMI).

Methods: We studied the sex-specific genetic contribution to knee OA surgery in a prospective cohort study of 62,490 twins aged 35 years or older with a follow-up period of up to 47 years (10,092 identical and 21,153 non-identical twin pairs, 54% women). To study interactions with age, we graphed the heritabilities over the lifespan for men and women. We also studied the sex-specific heritability across strata of the median BMI to explore any interactions with BMI.

Results: The overall heritability of knee OA surgery was 0.53 (95% confidence intervals [CI] = 0.31-0.75), with higher heritability among women (H2 = 0.80 (95% CI = 0.73-0.87)) than men (H2 = 0.39 (95% CI = 0.10-0.69)). For men, the heritability started to rise after age 68. The genetic contribution was particularly low in men above median BMI (H2≥23.7 kg/m2 = 0.08, 95% CI = -0.32-0.48). For women, the heritability was consistently high from age 50 to death, independently of BMI (H2≥22.5 kg/m2 = 0.77, 95% CI = 0.66-0.87).

Conclusion: There is a higher and more consistent genetic contribution for knee OA surgery in women than men. In men the genetic contribution was relatively low and varied with age and BMI.

Keywords: Gene-environment interaction; Genetics; Heritability; Knee osteoarthritis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Age Factors
  • Arthroplasty, Replacement, Knee / methods*
  • Body Mass Index*
  • Diseases in Twins*
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Middle Aged
  • Morbidity / trends
  • Osteoarthritis, Knee / epidemiology
  • Osteoarthritis, Knee / genetics*
  • Osteoarthritis, Knee / surgery
  • Osteotomy / methods*
  • Prognosis
  • Prospective Studies
  • Registries*
  • Sex Factors
  • Sweden / epidemiology
  • Young Adult