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Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis
A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto’s thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully un...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397507/ https://www.ncbi.nlm.nih.gov/pubmed/37545519 http://dx.doi.org/10.3389/fimmu.2023.1193293 |
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author | Zeber-Lubecka, Natalia Suchta, Katarzyna Kulecka, Maria Kluska, Anna Piątkowska, Magdalena Dabrowski, Michal J. Jankowska, Katarzyna Grymowicz, Monika Smolarczyk, Roman Hennig, Ewa E. |
author_facet | Zeber-Lubecka, Natalia Suchta, Katarzyna Kulecka, Maria Kluska, Anna Piątkowska, Magdalena Dabrowski, Michal J. Jankowska, Katarzyna Grymowicz, Monika Smolarczyk, Roman Hennig, Ewa E. |
author_sort | Zeber-Lubecka, Natalia |
collection | PubMed |
description | A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto’s thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (p(adjusted) < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases. |
format | Online Article Text |
id | pubmed-10397507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103975072023-08-04 Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis Zeber-Lubecka, Natalia Suchta, Katarzyna Kulecka, Maria Kluska, Anna Piątkowska, Magdalena Dabrowski, Michal J. Jankowska, Katarzyna Grymowicz, Monika Smolarczyk, Roman Hennig, Ewa E. Front Immunol Immunology A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto’s thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (p(adjusted) < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases. Frontiers Media S.A. 2023-07-20 /pmc/articles/PMC10397507/ /pubmed/37545519 http://dx.doi.org/10.3389/fimmu.2023.1193293 Text en Copyright © 2023 Zeber-Lubecka, Suchta, Kulecka, Kluska, Piątkowska, Dabrowski, Jankowska, Grymowicz, Smolarczyk and Hennig https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zeber-Lubecka, Natalia Suchta, Katarzyna Kulecka, Maria Kluska, Anna Piątkowska, Magdalena Dabrowski, Michal J. Jankowska, Katarzyna Grymowicz, Monika Smolarczyk, Roman Hennig, Ewa E. Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title | Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title_full | Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title_fullStr | Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title_full_unstemmed | Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title_short | Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto’s thyroiditis |
title_sort | exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and hashimoto’s thyroiditis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397507/ https://www.ncbi.nlm.nih.gov/pubmed/37545519 http://dx.doi.org/10.3389/fimmu.2023.1193293 |
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