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Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures

OBJECTIVES: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension. METHODS: We obtained genetic information from the Taiwan Biobank, including 88,3...

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Autores principales: Lai, Benjamin, Yu, Huang-Ping, Chang, Yu-Jing, Wang, Liang-Chin, Chen, Che-Kai, Zhang, Weiya, Doherty, Michael, Chang, Shang-Hung, Hsu, Jun-Te, Yu, Kuang-Hui, Kuo, Chang-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617405/
https://www.ncbi.nlm.nih.gov/pubmed/36309757
http://dx.doi.org/10.1186/s13075-022-02933-4
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author Lai, Benjamin
Yu, Huang-Ping
Chang, Yu-Jing
Wang, Liang-Chin
Chen, Che-Kai
Zhang, Weiya
Doherty, Michael
Chang, Shang-Hung
Hsu, Jun-Te
Yu, Kuang-Hui
Kuo, Chang-Fu
author_facet Lai, Benjamin
Yu, Huang-Ping
Chang, Yu-Jing
Wang, Liang-Chin
Chen, Che-Kai
Zhang, Weiya
Doherty, Michael
Chang, Shang-Hung
Hsu, Jun-Te
Yu, Kuang-Hui
Kuo, Chang-Fu
author_sort Lai, Benjamin
collection PubMed
description OBJECTIVES: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension. METHODS: We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates. RESULTS: Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03–1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02–1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout. CONCLUSIONS: In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02933-4.
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spelling pubmed-96174052022-10-30 Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures Lai, Benjamin Yu, Huang-Ping Chang, Yu-Jing Wang, Liang-Chin Chen, Che-Kai Zhang, Weiya Doherty, Michael Chang, Shang-Hung Hsu, Jun-Te Yu, Kuang-Hui Kuo, Chang-Fu Arthritis Res Ther Research OBJECTIVES: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension. METHODS: We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates. RESULTS: Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03–1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02–1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout. CONCLUSIONS: In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02933-4. BioMed Central 2022-10-29 2022 /pmc/articles/PMC9617405/ /pubmed/36309757 http://dx.doi.org/10.1186/s13075-022-02933-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lai, Benjamin
Yu, Huang-Ping
Chang, Yu-Jing
Wang, Liang-Chin
Chen, Che-Kai
Zhang, Weiya
Doherty, Michael
Chang, Shang-Hung
Hsu, Jun-Te
Yu, Kuang-Hui
Kuo, Chang-Fu
Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title_full Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title_fullStr Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title_full_unstemmed Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title_short Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
title_sort assessing the causal relationships between gout and hypertension: a bidirectional mendelian randomisation study with coarsened exposures
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617405/
https://www.ncbi.nlm.nih.gov/pubmed/36309757
http://dx.doi.org/10.1186/s13075-022-02933-4
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