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Genetic factors and osteoporotic fractures in elderly people

BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7250.1669 (Published 17 June 2000) Cite this as: BMJ 2000;320:1669

Twin data support genetic contribution to risk of fracture

  1. Alex J MacGregor, Arthritis Research Campaign senior fellow (alex.macgregor@kcl.ac.uk),
  2. Harold Snieder, genetic epidemiologist,
  3. Tim D Spector, director
  1. Twin Research and Genetic Epidemiology Unit, St Thomas's Hospital, London SE1 7EH
  2. Semmelweis University of Medicine, 2nd Department of Medicine, Budapest 1088, Hungary
  3. Free University Hospital, Amsterdam, Netherlands
  4. Accident and Trauma Research Centre, UKK Institute, PO Box 30, FIN-33501 Tampere, Finland
  5. Department of Public Health and General Practice, University of Oulu, FIN-90220 Oulu, Finland
  6. Department of Public Health, University of Turku, FIN-20520 Turku, Finland
  7. Accident and Trauma Research Centre, UKK Institute, PO Box 30, FIN-33501 Tampere
  8. Research Centre of Sports Medicine, UKK Institute, PO Box 30, FIN-33501 Tampere

    EDITOR—Kannus et al suggest from prospective data collected on Finnish twins that genetic factors are of only minor importance in explaining the population occurrence of osteoporotic fracture, particularly in women.1

    The evidence given to support this is the relatively small excess in concordance in monozygotic twins compared with dizygotic twins. But it is well recognised that twin concordances may be misleading unless the underlying prevalence of a disease is taken into account.2 For example, a small absolute difference in monozygotic compared with dizygotic concordance is more suggestive of a genetic effect for a trait that is relatively rare (such as fracture) than for one that is common. The data thus warrant closer scrutiny.

    We have estimated the relative contribution of genetic, shared environmental, and unique environmental components to the variation in susceptibility to fracture in these twins from the data provided. The analysis was conducted using a variance components approach with the statistical software Mx.3 The method assumes that risk of fracture is determined by a continuous underlying liability and is a plausible assumption for this trait.4

    As expected, the results show significant evidence of familial resemblance in the risk of fracture in both male and female twins. In female twins, despite the nationwide sampling frame, there is insufficient statistical power in this study to distinguish between models containing components in which this clustering is attributed to genetic factors alone, the shared family environment of the twins, or the combination of the two. In a model in which the only …

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