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

¹Department of Endocrinology and Metabolism, Odense University Hospital; ²The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark; ³Department of Statistics, University of Southern Denmark, Odense; and ⁴Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark

Submitted 3 July 2006 ; accepted in final form 6 November 2006

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 r_g = 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 r_e = 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.

thyroid-stimulating hormone; thyroid hormones; twin study; bivariate analyses

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