Twin Studies as a Model for Exploring the Aetiology of Autoimmune Thyroid Disease

Thomas Heiberg Brix; Laszlo Hegedüs


Clin Endocrinol. 2012;76(4):457-464. 

In This Article

Heritability of Autoimmune Thyroid Disease

During the last decades, twin studies have examined the impact of genetic factors in GD,[8,21,28] HT,[9] presence of thyroid autoantibodies in euthyroid subjects,[11,29,30] and distribution of TPOAb epitopic fingerprints.[31] The results from these studies are summarized in Fig. 1 and Table 1 . Because of major differences in the methods used for twin ascertainment, sample size, age and sex distribution, definitions of phenotypes (using different assays used for determination of thyroid autoantibodies) and evaluation of zygosity, it is not straight forward to compare the individual studies. However, despite these differences, a clear pattern emerges. Thus, most studies show significantly higher degrees of similarity in MZ than in DZ twins, confirming that genetic factors are of importance in the aetiology of these phenotypes.

Figure 1.

The relative importance of genetic and non-genetic factors in the aetiology of overt and subclinical autoimmune thyroid disease.

Using structural equation modelling, the heritability of GD and being thyroid autoantibody positive (TPOAb and/or positive TGAb) has been reported to be 79% (95% CI, 38–90%) and 73% (95% CI, 46–89%), respectively[8,11] (Fig. 1). Essentially, similar results were found when considering the serum concentrations of TPOAb and TGAb, Fig. 1. In other words, the relative impact of genetic factors in these phenotypes could be anywhere between 38% and 90%, but most likely it is around 75%. A further in-depth discussion of the identification, localization and characterization of this genetic contribution is beyond the scope of this review but these issues have been dealt with extensively in recent publications.[6,12,32]

Although the pronounced female predisposition to AITD, illustrated by a 5- to 10-fold higher prevalence in women,[33] has been known for over a century, the reason is still obscure. One of many suggested explanations for this phenomenon of female preponderance has been ascribed to sex chromosome differences between males and females and the possible interaction between gender and other genetic factors.[34] Unfortunately, only one twin study has had the power to further explore a possible genetic basis of the observed female preponderance in AITD.[11] In that study, we found no significant difference in the heritability estimates for TPOAb between males [61% (95% CI, 49–70%)] and females [72% (95% CI, 64–79%)]. In contrast, for TGAb concentrations, the heritability estimates were significantly different between males [39% (95% CI, 24–51%)] and females [75% (95%CI, 66–81%)]. Whether this reflects a genuine difference between males and females in the aetiology of harbouring TGAb remains to be established. By including opposite sex pairs in twin analyses, it is also possible to evaluate whether the same set of genes operate in males and females.[35] Using this approach, our data indicate that despite the aforementioned difference in the heritability of TGAb between males and females, it is the same set of genes that operate in males and females.[11] Whether this is also the case in clinically overt AITD, comprising GD and HT, is at present unknown.


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