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Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis
BACKGROUND: Although the association between hypothyroidism and idiopathic pulmonary fibrosis (IPF) is found in observational studies, it remains uncertain whether hypothyroidism causally influences IPF. METHODS: Two-sample Mendelian randomisation (MR) was conducted with hypothyroidism genome-wide a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586742/ https://www.ncbi.nlm.nih.gov/pubmed/34749302 http://dx.doi.org/10.1016/j.ebiom.2021.103669 |
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author | Zhang, Yanan Zhao, Meng Guo, Ping Wang, Yanjun Liu, Lu Zhao, Jinghua Gao, Ling Yuan, Zhongshang Xue, Fuzhong Zhao, Jiajun |
author_facet | Zhang, Yanan Zhao, Meng Guo, Ping Wang, Yanjun Liu, Lu Zhao, Jinghua Gao, Ling Yuan, Zhongshang Xue, Fuzhong Zhao, Jiajun |
author_sort | Zhang, Yanan |
collection | PubMed |
description | BACKGROUND: Although the association between hypothyroidism and idiopathic pulmonary fibrosis (IPF) is found in observational studies, it remains uncertain whether hypothyroidism causally influences IPF. METHODS: Two-sample Mendelian randomisation (MR) was conducted with hypothyroidism genome-wide association study (GWAS) data in the UK Biobank from 289,307 individuals (18,740 cases and 270,567 controls) and the largest GWAS summary statistics of IPF from 11,259 individuals (2,668 cases and 8,591 controls). Findings were verified using an independent validation dataset, as well as through different MR methods with different model assumptions. A multivariable MR based on Bayesian model averaging was further performed to evaluate whether hypothyroidism, even given several other comorbidities of IPF, remained to be the true causal one of IPF. FINDINGS: A positive causal effect of hypothyroidism on IPF was revealed (MR inverse-variance weighted [MR-IVW], odds ratio [OR]=1.125, 95% confidence interval [CI] 1.028-1.231; P=0.011), which was further verified in an independent validation set (MR-IVW, OR=1.229, 95% CI 1.054-1.432; P=0.008). The results were consistent from a variety of MR methods. Bidirectional analyses also indicated no reverse causation. Multivariable MR analysis showed hypothyroidism had the strongest marginal evidence (marginal inclusion probability=0.397, false discovery rate=0.025) compared with other comorbidities of IPF. INTERPRETATION: Our results illustrate the significant causal effect of hypothyroidism on IPF, which holds even given several other comorbidities of IPF. These findings may have an important insight into pathogenesis and possible future therapies of IPF. FUNDING: National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province and the Young Scholars Program of Shandong University. |
format | Online Article Text |
id | pubmed-8586742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85867422021-11-19 Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis Zhang, Yanan Zhao, Meng Guo, Ping Wang, Yanjun Liu, Lu Zhao, Jinghua Gao, Ling Yuan, Zhongshang Xue, Fuzhong Zhao, Jiajun EBioMedicine Research paper BACKGROUND: Although the association between hypothyroidism and idiopathic pulmonary fibrosis (IPF) is found in observational studies, it remains uncertain whether hypothyroidism causally influences IPF. METHODS: Two-sample Mendelian randomisation (MR) was conducted with hypothyroidism genome-wide association study (GWAS) data in the UK Biobank from 289,307 individuals (18,740 cases and 270,567 controls) and the largest GWAS summary statistics of IPF from 11,259 individuals (2,668 cases and 8,591 controls). Findings were verified using an independent validation dataset, as well as through different MR methods with different model assumptions. A multivariable MR based on Bayesian model averaging was further performed to evaluate whether hypothyroidism, even given several other comorbidities of IPF, remained to be the true causal one of IPF. FINDINGS: A positive causal effect of hypothyroidism on IPF was revealed (MR inverse-variance weighted [MR-IVW], odds ratio [OR]=1.125, 95% confidence interval [CI] 1.028-1.231; P=0.011), which was further verified in an independent validation set (MR-IVW, OR=1.229, 95% CI 1.054-1.432; P=0.008). The results were consistent from a variety of MR methods. Bidirectional analyses also indicated no reverse causation. Multivariable MR analysis showed hypothyroidism had the strongest marginal evidence (marginal inclusion probability=0.397, false discovery rate=0.025) compared with other comorbidities of IPF. INTERPRETATION: Our results illustrate the significant causal effect of hypothyroidism on IPF, which holds even given several other comorbidities of IPF. These findings may have an important insight into pathogenesis and possible future therapies of IPF. FUNDING: National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province and the Young Scholars Program of Shandong University. Elsevier 2021-11-05 /pmc/articles/PMC8586742/ /pubmed/34749302 http://dx.doi.org/10.1016/j.ebiom.2021.103669 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Zhang, Yanan Zhao, Meng Guo, Ping Wang, Yanjun Liu, Lu Zhao, Jinghua Gao, Ling Yuan, Zhongshang Xue, Fuzhong Zhao, Jiajun Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title | Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title_full | Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title_fullStr | Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title_full_unstemmed | Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title_short | Mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
title_sort | mendelian randomisation highlights hypothyroidism as a causal determinant of idiopathic pulmonary fibrosis |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586742/ https://www.ncbi.nlm.nih.gov/pubmed/34749302 http://dx.doi.org/10.1016/j.ebiom.2021.103669 |
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