Genome-Wide Analysis Identifies Two Susceptibility Loci for Positive Thyroid Peroxidase and Thyroglobulin Antibodies

Abstract Introduction Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indi...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism Jg. 105; H. 3; S. 944 - 951
Hauptverfasser: Matana, Antonela, Boutin, Thibaud, Torlak, Vesela, Brdar, Dubravka, Gunjača, Ivana, Kolčić, Ivana, Boraska Perica, Vesna, Punda, Ante, Polašek, Ozren, Barbalić, Maja, Hayward, Caroline, Zemunik, Tatijana
Format: Journal Article
Sprache:Englisch
Veröffentlicht: US Oxford University Press 01.03.2020
Copyright Oxford University Press
Schlagworte:
Adult
Aged
Antibodies
Autoantibodies - blood
Autoantibodies - genetics
Autoimmune diseases
Croatia
Female
Genetic factors
Genetic Loci
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Genomes
Humans
Interferon Regulatory Factors - genetics
Iodide peroxidase
Iodide Peroxidase - immunology
Male
Meta-analysis
Middle Aged
Proto-Oncogene Proteins c-yes - genetics
Thyroglobulin
Thyroglobulin - immunology
Thyroid diseases
Thyroid gland
Thyroiditis, Autoimmune - blood
Thyroiditis, Autoimmune - genetics
Thyroiditis, Autoimmune - immunology
Croatia
meta-analysis
thyroglobulin antibody
thyroid peroxidase antibody
genome-wide association study
ISSN:0021-972X, 1945-7197, 1945-7197
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Zusammenfassung:Abstract Introduction Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic influence; however, genetic factors that determine thyroid antibody positivity are largely unknown. Materials and Methods To identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2613 individuals from Croatia. Participants with elevated plasma TPOAb and/or TgAb were defined as cases (N = 619) and those with TPOAb and TgAb within reference values were defined as controls (N = 1994). Results We identified 2 novel loci, of which 1 is located within the YES1 gene (rs77284350, P = 1.50 × 10–8), and the other resides within the IRF8 gene (rs16939945, P = 5.04 × 10–8). Conclusions Although the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research.
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ISSN:0021-972X
1945-7197
1945-7197
DOI:10.1210/clinem/dgz239