The Genetics of AIS: A Twin Study

The pathogenesis of adolescent idiopathic scoliosis (AIS) has been associated with both genetic and environmental factors. Although most cases are sporadic about 25% of the patients are reported to have a positive family history. This together with other studies indicates a significant heritable component. Twins constitute a compelling natural experiment to establish the genetic contribution to AIS.

The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AIS.

Materials and Methods: The Danish Twin Register consists of all Danish twin pairs and the present cohort includes those born between 1931 and 1982. Establishment of zygosity has throughout the period been based on four questions of similarity with an accuracy of approximately 95%. In the spring of 2002 all registered twins received a 17-pages omnibus questionnaire. The total number of twins was 46,418. 34,944 (75.3%) representing 23,204 twin pairs answered the question ‘Have you been diagnosed with scoliosis?’ The overall prevalence of self reported scoliosis was calculated using the total number of answers as the general twin population. In an attempt to identify the twins most likely to suffer from AIS we excluded twins diagnosed before the age of 10 thus avoiding individuals with congenital deformities of the spine and with infantile or juvenile idiopathic scoliosis. Further we excluded individuals above the age of 50 at the time of the survey to avoid de novo scoliosis that commonly presents in the sixth decade. The pair-wise concordance estimates the probability that both twins are affected in a pair in which one is affected, while the proband-wise rate estimates the probability that a twin will be affected given that the partner is.

Concordance was compared using the Chi-square test. All scientific-ethical committees in Denmark have approved the study.

Results: 9,037 (54.5 %) females and 15,907 (45.5 %) males responded. The overall self reported prevalence of scoliosis was 1.36% (95% confidence limits (c.i.l.) 1.26-1.47), and stratified according to gender the male and a female prevalence was 0.96 (95% c.i.l. 0.80-1.14) and 1.71 % (95% c.i.l. 1.53-1.91) respectively. This difference was statistically significant (p<0 .001). The prevalence of AIS was not significantly different between monozygotic (MZ) and dizygotic (DZ) twins the figures were as would be expected from literature.

Of 11,740 twin pairs in whom both answered the above question 463 indicated that they had been diagnosed with scoliosis. The pair-wise concordance was 0.13 (95% c.i.l. 0.05-0.27) for MZ and zero (95% c.i.l. 0- 0.03) for DZ twin pairs, while the proband-wise concordance was 0.25 (95% c.i.l. 0.17-0.37) for MZ and zero in DZ twin pairs. This difference between MZ and DZ pairs was statistically significant (p<0 .05).

Conclusion: Our study confirms that the pathogenesis in AIS is complex and affected by both genetic and environmental factors. The higher concordance rate for MZ pairs confirms the contribution of the major genetic component while indicating the need to identify possible environmental triggers. The risk of developing scoliosis in a twin whose twin partner has scoliosis is less than believed hitherto.