To assess the relative genetic and environmental contribution to carpal tunnel syndrome (CTS) using a classic twin study of monozygotic (MZ) and dizygotic (DZ) twins. The study group comprised unselected female twin pairs, between 20 and 80 years of age, from the St Thomas' UK Adult Twin Registry. Individuals completed a questionnaire that included details on potential risk factors for CTS. The diagnosis of CTS was made using a standardized hand pain diagram and validated criteria. The genetic contribution to CTS was assessed using variance component and regression methods, the heritability was adjusted for environmental confounders. The role of individual risk factors was assessed by a nested case-control study. An overall prevalence of 14.2% for CTS was found in a population of 4,488 females, comprising 867 MZ and 970 DZ twin pairs, and 814 singletons. The concordance for CTS was significantly higher in MZ compared with DZ twins (case-wise concordance values of 0.35 and 0.24 respectively, with a significantly increased MZ:DZ ratio of 1.48; P = 0.03). Modeling produced a heritability estimate of 0.46 (95% CI 0.34-0.58) that was essentially unchanged after adjustment for environmental risk factors including age, body mass index, physical activities, and hormonal/reproductive factors. No major influence of any individual risk factor was seen in the case-control analysis of 520 cases and 3,154 controls, apart from a modest association with menopausal status with an increased risk of 1.53 and 1.43 in the peri and postmenopausal groups. There was no overall effect of age or body mass index. This is the first study to explore the genetic component of CTS. Our data show that up to half of the liability to CTS in women is genetically determined, and this appears to be the single strongest risk factor, with only minor contributions from known environmental factors. Further studies should focus on genetic mechanisms that may lead to tests for susceptibility and detection of those at risk of developing CTS.
