Heritability of thyroid peroxidase autoantibody levels in type 1 diabetes: evidence from discordant twin pairs

• Published in: Diabetologia 2015-09, Vol.58 (9), p.2079-2086
• Main Authors: Wang, Bin, Hawa, Mohammed I., Rijsdijk, Frühling V., Fain, Pamela R., Paschou, Stavroula A., Boehm, Bernhard O., Steck, Andrea K., Snieder, Harold, Leslie, R. David G.
• Format: Article
• Language: English
• Subjects: Adolescent; Autoantibodies - blood; Autoantibodies - immunology; Autoantigens - blood; Autoantigens - immunology; Autoimmune diseases; Autoimmunity; Child; Cohort Studies; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Disease; Environment; Epidemiology; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Human Physiology; Humans; Internal Medicine; Iodide Peroxidase - blood; Iodide Peroxidase - immunology; Iron-Binding Proteins - blood; Iron-Binding Proteins - immunology; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Quantitative genetics; Radioimmunoassay; Thyroid gland; Thyroid Gland - immunology; Twin studies; Twins; Twins, Dizygotic; Twins, Monozygotic; United Kingdom; United States
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-015-3664-y

Aims/hypothesis The discordance status of (autoimmune) type 1 diabetes within monozygotic twin pairs points to the importance of environmental factors. The aim of this study was to investigate whether the environmental events causing type 1 diabetes influence thyroid autoimmunity. Methods Monozygotic and dizygotic twins discordant for type 1 diabetes from the UK and USA were tested for thyroid peroxidase autoantibodies (TPOA) by radioimmunoassay. Using quantitative genetic model fitting of a liability-threshold model we estimated the contribution of genetic (heritability) and environmental factors to TPOA. Results TPOA positivity was higher in females than in males in both cohorts and was associated with later age at diagnosis in the UK and combined cohorts ( p   0.2 in all groups). The best-fitting models showed heritability (95% CI) estimates for TPOA of 63% (37%, 80%) for the UK and 80% (51%, 92%) for US twins, while the best-fitting meta-analysis model of the two twin cohorts combined included additive genetic and unique environmental factors with a heritability estimate of 69% (50%, 82%). Conclusions/interpretation Risk of thyroid autoimmunity, defined by TPOA, in the context of autoimmune diabetes is, substantially, genetically determined in discordant twin pairs. Environmental factors leading to type 1 diabetes were not the same as those involved with thyroid autoimmunity. It follows that it is as important to investigate for thyroid autoimmunity in relatives of type 1 diabetes patients as it is in the patients themselves.