Autoimmune Thyroiditis and Diabetes: Dissecting the Joint Genetic Susceptibility in a Large Cohort of Multiplex Families

Villano, Maria Justina B.; Huber, Amanda K.; Greenberg, David A.; Golden, Brian K.; Concepcion, Erlinda; Tomer, Yaron

doi:10.1210/jc.2008-2193

Cited by 96 publications

(99 citation statements)

References 33 publications

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“…results were also consistent with the previously reported weak associations at candidate genes in the T1D family data set [Villano et al, 2009]. LD epistasis analysis indicated that some additional genes might be potentially associated with the T1D phenotype.…”

Section: Wellcome Trust Case Control Consortium 2007] Based On Trendsupporting

confidence: 92%

“…Multipoint genome-wide linkage scan under the PPL framework was conducted on the T1D family dataset to be used later for the combined study. The PPL treats trait parameters as nuisance parameters and integrates them out, rather than restricting analysis to the two genetic models used in the original study [Villano et al, 2009]. Results (not shown) of two-point fixed model runs using the models provided in the original paper yielded slightly different results from those reported in Villano, which was expected due to our additional data cleaning.…”

Section: Discussionmentioning

confidence: 93%

“…The family dataset used here is described in detail elsewhere [Villano et al, 2009]. Data were kindly provided for this dissertation by the principle investigator on the project, Dr. Yaron Tomer.…”

Section: T1d Family Datasetmentioning

confidence: 99%

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Association statistics under the PPL framework

Huang

Vieland

2010

Genetic Epidemiology

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In this dissertation, the posterior probability of linkage (PPL) framework is extended to the analysis of case-control (CC) data and three new linkage disequilibrium (LD) statistics are introduced. These statistics measure the evidence for or against LD, rather than testing the null hypothesis of no LD, and they therefore avoid the need for multiple testing corrections. They are suitable not only for CC designs but also can be used in application to family data, ranging from trios to complex pedigrees, all under the same statistical framework, allowing for the unified analysis of these disparate data structures. They also provide the other core advantages of the PPL framework, including the use of sequential updating to accumulate LD evidence across potentially heterogeneous sets of subsets of data; parameterization in terms of a very general trait likelihood, which simultaneously considers dominant, recessive, and additive models; and a straightforward mechanism for modeling two-locus epistasis. Finally, being implemented within the PPL framework, the new statistics readily allow linkage information obtained from distinct data, to be incorporated into LD analyses in the form of a prior probability distribution. Performance of the proposed LD statistics is examined using simulated data. In addition, the effects of key modeling violations on performance are assessed. These statistics are also applied to a previously published type 1 diabetes (T1D) family dataset with a few candidate genes with previously reported weak associations, and another T1D CC dataset also previously published as a genome-wide association (GWA) study with some strong associations reported. The new LD statistics under the PPLD framework confirm most of the findings in the published work and also find some new SNPs suspected of being associated with T1D. Sequential updating between the family dataset and the CC dataset dramatically increased the association signal strength for a CTLA4 SNP genotyped in both studies. Linkage information gleaned from the family dataset is also combined into the LD analysis of the CC dataset 2 to demonstrate the utility of this unique feature of the PPL framework, and specifically for the new LD statistics.Abstract Approved: ____________________________________ Thesis Supervisor

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Section: Wellcome Trust Case Control Consortium 2007] Based On Trendsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 93%

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Association statistics under the PPL framework

Huang

Vieland

2010

Genetic Epidemiology

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“…However, some authors have found a positive association between GADA and ATD (2,3,7,10,(22)(23)(24)(25). Bonifacio and cols.…”

Section: Discussionmentioning

confidence: 94%

Thyroid disorders are common in first-degree relatives of individuals with type 1 diabetes mellitus

Araújo

Barone

Melleti

et al. 2015

Arch. Endocrinol. Metab.

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Objective: Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Subjects and me thods: Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. Results: We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Conclusions: Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals. Arch Endocrinol Metab. 2015;59(2):112-5

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“…There are several hypotheses explaining the development of different components of APS III [1,[10][11][12][13][14][15][16]. The most widely accepted is the autoimmune genetic hypothesis, assuming involvement of genes associated with immune regulation [17].…”

Section: Discussionmentioning

confidence: 99%

Przypadek pokrzywki autoimmunologicznej współistniejącej z autoimmunologicznym zespołem wielogruczołowym typu III związanym z chorobą Hashimoto, cukrzycą typu 1 i bielactwem

Kasznicki¹,

Drzewoski²

2014

Endokrynologia Polska

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We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs. Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.

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Autoimmune Thyroiditis and Diabetes: Dissecting the Joint Genetic Susceptibility in a Large Cohort of Multiplex Families

Abstract: Our results demonstrate a strong shared genetic susceptibility to T1D and AITD, with most shared genes involved in immune regulation, suggesting that immune dysregulation plays an important role in the joint susceptibility to T1D and AITD.

Cited by 96 publications

References 33 publications

Association statistics under the PPL framework

Association statistics under the PPL framework

Thyroid disorders are common in first-degree relatives of individuals with type 1 diabetes mellitus

Przypadek pokrzywki autoimmunologicznej współistniejącej z autoimmunologicznym zespołem wielogruczołowym typu III związanym z chorobą Hashimoto, cukrzycą typu 1 i bielactwem

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