Twin studies as a model for exploring the aetiology of autoimmune thyroid disease

Abstract

SummaryTwins are an important resource for evaluating the relative contribution of genetic and environmental factors in determining a phenotype. During the last decades, a number of twin studies have investigated the aetiology of several phenotypes related to thyroid autoimmunity. Taken together, these studies have provided valid and unbiased information regarding the influence of genetic and environmental factors in the aetiology of autoimmune thyroid disease (AITD). The comparison of concordance rates between monozygotic (MZ) and dizygotic twins provides irrefutable evidence of a genetic component, and biometric twin modelling shows that approximately 75% of the total phenotypic variance in AITD is because of genetic effects. On the other hand, the lack of complete concordance in MZ twin pairs is proof of environmental and/or epigenetic factors also playing an important role. The impact of environmental triggers such as cigarette smoking, birth characteristics, infection with Yersinia enterocolitica, microchimerism and degree of X chromosome inactivation (XCI) has been evaluated by investigating AITD discordant twin pairs. These studies indicate that smoking, Y. enterocolitica infection and skewed XCI may be causally associated with clinically overt AITD, but not with the presence of thyroid autoantibodies in euthyroid subjects. Microchimerism, but not birth weight, might play a role in AITD. Twin studies offer several features that uniquely enhance our ability to localize genes and understand their function. Future twin studies should incorporate information on genetic, epigenetic and environmental variation thereby enhancing our ability to quantify the precise effect of specific risk factors.

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

“…Combining the effects of four HLA loci and five non-HLA loci, they accounted for only 9.3% of heritability of Graves' disease in a Chinese study (33). Twin studies have convincingly demonstrated that genetic factors contribute about 70% to the development of AITD, leaving only 30% for environmental factors (34). The data strongly suggest that there must be many more still undetected susceptibility genes, each variant contributing just a little to the development of AITD.…”

Yersinia enterocolitica Provides the Link between Thyroid-Stimulating Antibodies and Their Germline Counterparts in Graves’ Disease

“…Danish twin studies have estimated 25% of the predisposition to Graves' disease to be contributed by environmental factors (18). Infection with the bacterium Yersinia enterocolitica has been implicated in the pathogenesis of Graves' disease since the 1970s (19)(20)(21).…”

Association of candidate gene polymorphisms for autoimmune thyroid diseases in patients with familial diffuse toxic goiter and autoimmune thyroiditis

“…Brix и соавт. оценили вели-чину генетического компонента в развитии АИЗ ЩЖ, равную 75% [3]. Работы, связанные с полноге-номным скринингом, позволили установить гены-кандидаты, предрасполагающие к развитию АИЗ ЩЖ, которые можно разделить на три типа: тирео-идспецифические гены, гены системы HLA, не-HLA иммунорегуляторные гены [4].…”