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

Wang, Bin; Hawa, M.; Rijsdijk, Frühling; Fain, Pamela R.; Paschou, Stavroula Α.; Boehm, Bernhard O.; Steck, Andrea K.; Snieder, Harold; Leslie, Richard

doi:10.1007/s00125-015-3664-y

Cited by 6 publications

(5 citation statements)

References 19 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the environmental overlap was large, with 10–18% of the variance attributable to factors shared across the disorders but unique to individuals. Our findings contrast with results from a co-twin control analysis by Wang et al ( 33 ) that did not find evidence of association between type 1 diabetes and thyroid peroxidase autoantibodies (TPOab) over and above shared factors in twin pairs (i.e. shared genetic and environmental influences).…”

Section: Discussioncontrasting

confidence: 99%

Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

Skov

Kuja‐Halkola

Magnusson

et al. 2022

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases, and to quantify shared genetic and environmental factors. Design Twin cohort study Methods National health registers were used to identify cases among 110,814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and vice-versa. Variance explained by genetics (i.e., heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results Individuals with one disease were at a high risk for the other disease (adjusted risk ratio 11.4 [95% CI, 8.5-15.3]). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI, 3.2-15.1) and 1.7 (95% CI, 0.7-4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis. Conclusions Both genes and environment unique to individual twins contribute to a considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering, and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets.

show abstract

Section: Discussioncontrasting

confidence: 99%

Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

Skov

Kuja‐Halkola

Magnusson

et al. 2022

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Of interest, the risk for TPOA in adolescence was increased if children had developed IA or TGA and remained increased in children with the high-risk HLA genotypes, suggesting some, but incomplete, overlap in genetic and environmental determinants of the autoantibodies. This is consistent with previous twin studies that showed that heritability of thyroid autoimmunity is .50% (31,32) and that heritability includes additive genetic factors and environmental factors that are different for TPOA compared with IA (31).…”

Section: Discussionsupporting

confidence: 92%

Age, HLA, and Sex Define a Marked Risk of Organ-Specific Autoimmunity in First-Degree Relatives of Patients With Type 1 Diabetes

et al. 2019

View full text Add to dashboard Cite

Autoimmune diseases can be diagnosed early through the detection of autoantibodies. The aim of this study was to determine the risk of organ-specific autoimmunity in individuals with a family history of type 1 diabetes. RESEARCH DESIGN AND METHODS The study cohort included 2,441 first-degree relatives of patients with type 1 diabetes who were prospectively followed from birth to a maximum of 29.4 years (median 13.2 years). All were tested regularly for the development of autoantibodies associated with type 1 diabetes (islet), celiac disease (transglutaminase), or thyroid autoimmunity (thyroid peroxidase). The outcome was defined as an autoantibody-positive status on two consecutive samples. RESULTS In total, 394 relatives developed one (n = 353) or more (n = 41) of the three diseaseassociated autoantibodies during follow-up. The risk by age 20 years was 8.0% (95% CI 6.8-9.2%) for islet autoantibodies, 6.3% (5.1-7.5%) for transglutaminase autoantibodies, 10.7% (8.9-12.5%) for thyroid peroxidase autoantibodies, and 21.5% (19.5-23.5%) for any of these autoantibodies. Each of the three disease-associated autoantibodies was defined by distinct HLA, sex, genetic, and age profiles. The risk of developing any of these autoantibodies was 56.5% (40.8-72.2%) in relatives with HLA DR3/DR3 and 44.4% (36.6-52.2%) in relatives with HLA DR3/DR4-DQ8. CONCLUSIONS Relatives of patients with type 1 diabetes have a very high risk of organ-specific autoimmunity. Appropriate counseling and genetic and autoantibody testing for multiple autoimmune diseases may be warranted for relatives of patients with type 1 diabetes. Prospective studies that follow children from birth have established that autoimmunity can start very early in life and years before clinical symptoms appear (1-3). In type 1 diabetes, autoimmunity often appears between 6 months and 3 years of age (1-3), and the large majority of children who develop autoantibodies against multiple pancreatic islet antigens at this age progress to clinical disease (4). New disease paradigms have emerged from such studies, leading to extensive screening (5), the

show abstract

“…While ADM is a major component of the organ‐specific autoimmune disease group, we know little of the risk of autoimmunity in Chinese patients and how it predisposes to other autoimmune diseases. As with studies in white populations, TPO autoantibody positivity was higher both in people with ADM (17.7%) and, in particular, in women, whether they had ADM or not (22.1%) . To date, data on 21‐OH and tTG autoantibodies in ADM are scarce, both in China and elsewhere.…”

Section: Discussionmentioning

confidence: 82%

“…As with studies in white populations, 12,14 TPO autoantibody positivity was higher both in people with ADM (17.7%) and, in particular, in women, whether they had ADM or not (22.1%). 27 To date, data on 21-OH and tTG autoantibodies in ADM are scarce, both in China and elsewhere. The biopsy-positive and serum-positive prevalence of coeliac disease tend to be low among Asians in general (0.5% and 1.6%, respectively) 28 , while autoimmunity (positive results in assays for anti-tTG IgA and anti-DGP-IgG) was only 0.06%.…”

Section: The Prevalence Of T1d In China Differs From Western Countries;mentioning

confidence: 99%

Identification of autoimmune type 1 diabetes and multiple organ‐specific autoantibodies in adult‐onset non‐insulin‐requiring diabetes in China: A population‐based multicentre nationwide survey

Xiang

Huang

Zhu

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). Materials and methods:We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT.Results: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio[OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001).Conclusions: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations. K E Y W O R D Stype 1 diabetes, autoimmune diabetes, GAD-Ab, IA2-Ab, ZnT8-Ab, TPO-Ab, tTG-Ab, 21- OH-Ab

show abstract

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

Cited by 6 publications

References 19 publications

Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

Age, HLA, and Sex Define a Marked Risk of Organ-Specific Autoimmunity in First-Degree Relatives of Patients With Type 1 Diabetes

Identification of autoimmune type 1 diabetes and multiple organ‐specific autoantibodies in adult‐onset non‐insulin‐requiring diabetes in China: A population‐based multicentre nationwide survey

Contact Info

Product

Resources

About