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Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study

BACKGROUND: Meta-analysis of genome-wide association studies (GWAS) data showed that the relationship between hypothyroidism and rheumatoid arthritis (RA) risk remains under debate. This study is conducted to test the causal relationship of hypothyroidism and RA. METHODS: A two-sample Mendelian rand...

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Autores principales: Gao, Yang, Fan, Zheng-Rui, Shi, Fang-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262846/
https://www.ncbi.nlm.nih.gov/pubmed/37324262
http://dx.doi.org/10.3389/fendo.2023.1179656
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author Gao, Yang
Fan, Zheng-Rui
Shi, Fang-Yuan
author_facet Gao, Yang
Fan, Zheng-Rui
Shi, Fang-Yuan
author_sort Gao, Yang
collection PubMed
description BACKGROUND: Meta-analysis of genome-wide association studies (GWAS) data showed that the relationship between hypothyroidism and rheumatoid arthritis (RA) risk remains under debate. This study is conducted to test the causal relationship of hypothyroidism and RA. METHODS: A two-sample Mendelian randomization (TSMR) analysis was employed to estimate the causality of hypothyroidism and rheumatoid arthritis in European ancestry and Asian ancestry. Integrating the effects generated by TSMR, functional annotations and noncoding variant prediction framework were applied to analyze and interpret the functional instrument variants (IVs). RESULTS: The results of the inverse variance weighted method showed a strong significant causal relationship between hypothyroidism and risk of RA in European ancestry [odds ratio (OR) = 1.96; 95% confidence interval (CI) 1.49, 2.58; p < 0.001]. The outcomes of MR-Egger, weighted median, weighted mode, and simple mode also showed that hypothyroidism was significantly associated with increased risk of RA in European ancestry. The MR-PRESSO method also showed significant results [Outlier-corrected Causal Estimate = 0.70; standard error (SE) = 0.06; p < 0.001]. An independent dataset and an Asian ancestry dataset were applied to estimate and obtain the coincident results. Furthermore, we integrated the effect of variants in TSMR analysis, functional annotations, and prediction methods to pinpoint the single-nucleotide polymorphism (SNP) rs4409785 as one of the causal variants, which suggested that this variant could impact the binding of CTCF-cohesin and play a vital role in immune cells. CONCLUSION: In this study, we prove that hypothyroidism is significantly causally associated with increased RA risk, which has not been shown in previous studies. Furthermore, we pinpoint the potential causal variants in RA.
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spelling pubmed-102628462023-06-15 Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study Gao, Yang Fan, Zheng-Rui Shi, Fang-Yuan Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Meta-analysis of genome-wide association studies (GWAS) data showed that the relationship between hypothyroidism and rheumatoid arthritis (RA) risk remains under debate. This study is conducted to test the causal relationship of hypothyroidism and RA. METHODS: A two-sample Mendelian randomization (TSMR) analysis was employed to estimate the causality of hypothyroidism and rheumatoid arthritis in European ancestry and Asian ancestry. Integrating the effects generated by TSMR, functional annotations and noncoding variant prediction framework were applied to analyze and interpret the functional instrument variants (IVs). RESULTS: The results of the inverse variance weighted method showed a strong significant causal relationship between hypothyroidism and risk of RA in European ancestry [odds ratio (OR) = 1.96; 95% confidence interval (CI) 1.49, 2.58; p < 0.001]. The outcomes of MR-Egger, weighted median, weighted mode, and simple mode also showed that hypothyroidism was significantly associated with increased risk of RA in European ancestry. The MR-PRESSO method also showed significant results [Outlier-corrected Causal Estimate = 0.70; standard error (SE) = 0.06; p < 0.001]. An independent dataset and an Asian ancestry dataset were applied to estimate and obtain the coincident results. Furthermore, we integrated the effect of variants in TSMR analysis, functional annotations, and prediction methods to pinpoint the single-nucleotide polymorphism (SNP) rs4409785 as one of the causal variants, which suggested that this variant could impact the binding of CTCF-cohesin and play a vital role in immune cells. CONCLUSION: In this study, we prove that hypothyroidism is significantly causally associated with increased RA risk, which has not been shown in previous studies. Furthermore, we pinpoint the potential causal variants in RA. Frontiers Media S.A. 2023-05-30 /pmc/articles/PMC10262846/ /pubmed/37324262 http://dx.doi.org/10.3389/fendo.2023.1179656 Text en Copyright © 2023 Gao, Fan and Shi 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 Endocrinology
Gao, Yang
Fan, Zheng-Rui
Shi, Fang-Yuan
Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title_full Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title_fullStr Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title_full_unstemmed Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title_short Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study
title_sort hypothyroidism and rheumatoid arthritis: a two-sample mendelian randomization study
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262846/
https://www.ncbi.nlm.nih.gov/pubmed/37324262
http://dx.doi.org/10.3389/fendo.2023.1179656
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