Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population

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. The aim of this study was 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; 1,380 healthy euthyroid Danish twins (284 monozygotic, 286 dizygotic, 120 opposite-sex twin pairs) were recruited. Genetic and environmental associations between thyroid function measurements were examined using quantitative genetic modeling. In bivariate genetic models, the phenotypic relation between two measurements was divided into genetic and environmental correlations. 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%. Only 7% of the genetic component of serum free T3 levels is shared with serum free T4. Serum TSH and thyroid hormone levels did not share any genetic influences. In conclusion, thyroid hormone levels are partly genetically correlated genes that affect free T4 levels and exert pleiotropic effects on free T3 levels, although most of the genetic variance for these measurements is trait specific.