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

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...

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Published inThe journal of clinical endocrinology and metabolism Vol. 105; no. 3; p. 944
Main Authors Matana, Antonela, Boutin, Thibaud, Torlak, Vesela, Brdar, Dubravka, Gunjaca, Ivana, Kolcic, Ivana, Perica, Vesna Boraska, Punda, Ante, Polasek, Ozren, Barbalic, Maja, Hayward, Caroline, Zemunik, Tatijana
Format Journal Article
LanguageEnglish
Published Oxford University Press 01.03.2020
Subjects
Care and treatment
Diagnosis
Genetic aspects
Genetic research
Genetic susceptibility
Genetic variation
Health aspects
Immune response
Thyroid diseases
Croatia
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Summary: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 infuence; 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. (J Clin Endocrinol Metab 105: 944-951, 2020) Key Words: genome-wide association study, meta-analysis, thyroid peroxidase antibody, thyroglobulin antibody
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgz239