Submitted on July 3, 2006
Accepted on November 6, 2006
Genetic and environmental interrelations between measures of thyroid function in a healthy Danish twin population
Pia Skov Hansen1*, Thomas Heiberg Brix2, Ivan Iachine3, Thorkild IA Sørensen4, Kirsten Ohm Kyvik5, and Laszlo Hegedüs6
1 Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark; The Danish Twin Registry, Institute of Public Health, Epidemiology, University of Southern Denmark, Odense, Denmark
2 Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
3 Department of Statistics, University of Southern Denmark, Odense, Denmark
4 Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Odense, Denmark
5 The Danish Twin Registry, Institute of Public Health, Epidemiology, University of Southern Denmark, Odense, Denmark
6 Odense, Denmark; Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
* To whom correspondence should be addressed. E-mail: piaskovhansen{at}dadlnet.dk.
Context: Serum thyrotropin (TSH), free thyroxine (T4) and free triiodothyronine (T3) levels illustrate the thyroid function set-point, but the interrelations between these have never been characterized in detail.
Aim: To examine the associations between TSH and thyroid hormone levels in healthy euthyroid twins, and to determine the extent to which the same genes influence more than one of these biochemical traits.
Methods: 1380 healthy, euthyroid Danish twins (284 monozygotic, 286 dizygotic and 120 opposite sex twin pairs) were recruited. Genetic and environmental associations between the thyroid function measurements were examined using quantitative genetic modelling. In bivariate genetic models, the phenotypic relationship between two measurements was divided into genetic and environmental correlations.
Results: Free T4 and free T3 levels were positively correlated r = 0.32, p<0.0001. The genetic correlation between serum free T4 and free T3 levels was rg = 0.25 (95% CI 0.14-0.35), suggesting that a set of common genes affect both phenotypes (pleiotropy). The correlation between the environmental effects was re=0.41 (0.32-0.50). From this we calculated that the proportion of the correlation between free T4 and free T3 levels mediated by common genetic factors was 48%. In contrast, only 7% of the genetic component of free T3 levels was shared with free T4 levels. Serum TSH and thyroid hormone levels did not share any genetic influences.
Conclusion: Thyroid hormone levels are partly genetically correlated. However, most of the genetic variance for these measures is trait specific.
