Cargando…

Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis

Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid...

Descripción completa

Detalles Bibliográficos
Autores principales: Brčić, Luka, Barić, Ana, Gračan, Sanda, Torlak, Vesela, Brekalo, Marko, Škrabić, Veselin, Zemunik, Tatijana, Barbalić, Maja, Punda, Ante, Boraska Perica, Vesna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440971/
https://www.ncbi.nlm.nih.gov/pubmed/30926877
http://dx.doi.org/10.1038/s41598-019-41850-6
_version_ 1783407461577785344
author Brčić, Luka
Barić, Ana
Gračan, Sanda
Torlak, Vesela
Brekalo, Marko
Škrabić, Veselin
Zemunik, Tatijana
Barbalić, Maja
Punda, Ante
Boraska Perica, Vesna
author_facet Brčić, Luka
Barić, Ana
Gračan, Sanda
Torlak, Vesela
Brekalo, Marko
Škrabić, Veselin
Zemunik, Tatijana
Barbalić, Maja
Punda, Ante
Boraska Perica, Vesna
author_sort Brčić, Luka
collection PubMed
description Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid diseases. We performed the first genome-wide association analysis of thyroid antibodies in 430 HT patients that may be considered as population extremes for thyroid antibodies distribution. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P = 2.34 × 10(−7)) and rs756763 inside CA10 (P = 6.05 × 10(−7)), and one with TPOAb, rs12507813 positioned between TRIM61 and TRIM60 (P = 4.95 × 10(−7)). Bivariate analysis resulted with three suggestively associated genetic variants that predispose to both antibodies: rs13190616 inside RP11-138J23.1 (P = 2.01 × 10(−6)), rs561030786 close to DUBR (P = 7.33 × 10(−6)) and rs12713034 inside FSHR (P = 7.66 × 10(−6)). All identified genomic regions have a substantial literature record of involvement with female-related traits, immune-mediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and different non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function.
format Online
Article
Text
id pubmed-6440971
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64409712019-04-04 Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis Brčić, Luka Barić, Ana Gračan, Sanda Torlak, Vesela Brekalo, Marko Škrabić, Veselin Zemunik, Tatijana Barbalić, Maja Punda, Ante Boraska Perica, Vesna Sci Rep Article Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid diseases. We performed the first genome-wide association analysis of thyroid antibodies in 430 HT patients that may be considered as population extremes for thyroid antibodies distribution. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P = 2.34 × 10(−7)) and rs756763 inside CA10 (P = 6.05 × 10(−7)), and one with TPOAb, rs12507813 positioned between TRIM61 and TRIM60 (P = 4.95 × 10(−7)). Bivariate analysis resulted with three suggestively associated genetic variants that predispose to both antibodies: rs13190616 inside RP11-138J23.1 (P = 2.01 × 10(−6)), rs561030786 close to DUBR (P = 7.33 × 10(−6)) and rs12713034 inside FSHR (P = 7.66 × 10(−6)). All identified genomic regions have a substantial literature record of involvement with female-related traits, immune-mediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and different non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function. Nature Publishing Group UK 2019-03-29 /pmc/articles/PMC6440971/ /pubmed/30926877 http://dx.doi.org/10.1038/s41598-019-41850-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Brčić, Luka
Barić, Ana
Gračan, Sanda
Torlak, Vesela
Brekalo, Marko
Škrabić, Veselin
Zemunik, Tatijana
Barbalić, Maja
Punda, Ante
Boraska Perica, Vesna
Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title_full Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title_fullStr Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title_full_unstemmed Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title_short Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
title_sort genome-wide association analysis suggests novel loci underlying thyroid antibodies in hashimoto’s thyroiditis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440971/
https://www.ncbi.nlm.nih.gov/pubmed/30926877
http://dx.doi.org/10.1038/s41598-019-41850-6
work_keys_str_mv AT brcicluka genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT baricana genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT gracansanda genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT torlakvesela genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT brekalomarko genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT skrabicveselin genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT zemuniktatijana genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT barbalicmaja genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT pundaante genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis
AT boraskapericavesna genomewideassociationanalysissuggestsnovellociunderlyingthyroidantibodiesinhashimotosthyroiditis