The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins

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Abstract
Objective: In euthyroid individuals, autoantibodies to thyroid peroxidase (TPOab) and thyroglobulin (Tgab) are regarded as early markers of thyroid autoimmunity. Family and twin studies suggest that development of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is under genetic influence. We aimed to estimate the relative importance of genetic and environmental effects for the presence of thyroid autoantibodies in euthyroid subjects. Methods: A representative sample of healthy twin pairs was identified through the Danish Twin Registry; 1372 individuals, divided into 283 monozygotic (MZ), 285 dizygotic same sex (DZ), and 118 opposite sex twin pairs were investigated. Serum TPOab and serum Tgab were measured. Proband-wise concordance and intraclass correlations were calculated, and quantitative genetic modelling was performed. Results: Probandwise concordance and intraclass correlations were consistently higher for MZ than for DZ twin pairs indicating genetic influence. Genetic components (with 95% confidence intervals) accounted for 73% (46–89%) of the liability of being thyroid antibody positive. Adjusting for covariates (age, TSH and others), the estimate for genetic influence on serum TPOab concentrations was 61% (49–70%) in males and 72% (64–79%) in females. For serum Tgab concentrations, the estimates were 39% (24–51%) and 75% (66–81%) respectively. Conclusions: Early markers of thyroid autoimmunity appear to be under strong genetic influence. The analyses suggest that it is the same set of genes that operate in males and females. However, complex mechanisms such as dominance and/or epistasis may be involved. Abstract Objective: In euthyroid individuals, autoantibodies to thyroid peroxidase (TPOab) and thyroglobulin (Tgab) are regarded as early markers of thyroid autoimmunity. Family and twin studies suggest that development of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is under genetic influence. We aimed to estimate the relative importance of genetic and environmental effects for the presence of thyroid autoantibodies in euthyroid subjects. Methods: A representative sample of healthy twin pairs was identified through the Danish Twin Registry; 1372 individuals, divided into 283 monozygotic (MZ), 285 dizygotic same sex (DZ), and 118 opposite sex twin pairs were investigated. Serum TPOab and serum Tgab were measured. Proband-wise concordance and intraclass correlations were calculated, and quantitative genetic modelling was performed. Results: Probandwise concordance and intraclass correlations were consistently higher for MZ than for DZ twin pairs indicating genetic influence. Genetic components (with 95% confidence intervals) accounted for 73% (46–89%) of the liability of being thyroid antibody positive. Adjusting for covariates (age, TSH and others), the estimate for genetic influence on serum TPOab concentrations was 61% (49–70%) in males and 72% (64–79%) in females. For serum Tgab concentrations, the estimates were 39% (24–51%) and 75% (66–81%) respectively. Conclusions: Early markers of thyroid autoimmunity appear to be under strong genetic influence. The analyses suggest that it is the same set of genes that operate in males and females. However, complex mechanisms such as dominance and/or epistasis may be involved.