Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
Abstract 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, includi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02933-4 |
| _version_ | 1811198143663964160 |
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| author | Benjamin Lai Huang-Ping Yu Yu-Jing Chang Liang-Chin Wang Che-Kai Chen Weiya Zhang Michael Doherty Shang-Hung Chang Jun-Te Hsu Kuang-Hui Yu Chang-Fu Kuo |
| author_facet | Benjamin Lai Huang-Ping Yu Yu-Jing Chang Liang-Chin Wang Che-Kai Chen Weiya Zhang Michael Doherty Shang-Hung Chang Jun-Te Hsu Kuang-Hui Yu Chang-Fu Kuo |
| author_sort | Benjamin Lai |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T01:25:49Z |
| format | Article |
| id | doaj.art-e0217623945e48c6ad014aa007c54226 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-12T01:25:49Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-e0217623945e48c6ad014aa007c542262022-12-22T03:53:39ZengBMCArthritis Research & Therapy1478-63622022-10-0124111210.1186/s13075-022-02933-4Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposuresBenjamin Lai0Huang-Ping Yu1Yu-Jing Chang2Liang-Chin Wang3Che-Kai Chen4Weiya Zhang5Michael Doherty6Shang-Hung Chang7Jun-Te Hsu8Kuang-Hui Yu9Chang-Fu Kuo10Center for Artificial Intelligence in Medicine, Chang Gung Memorial HospitalDepartment of Anesthesiology, Chang Gung Memorial HospitalCenter for Artificial Intelligence in Medicine, Chang Gung Memorial HospitalDivision of Rheumatology, Allergy and Immunology, Chang Gung Memorial HospitalCenter for Artificial Intelligence in Medicine, Chang Gung Memorial HospitalAcademic Rheumatology, School of Medicine, University of NottinghamAcademic Rheumatology, School of Medicine, University of NottinghamDivision of Cardiology, Chang Gung Memorial Hospital, Linkou Medical CenterDepartment of General Surgery, Gung Memorial Hospital at Linkou, Chang Gung University College of MedicineDivision of Rheumatology, Allergy and Immunology, Chang Gung Memorial HospitalCenter for Artificial Intelligence in Medicine, Chang Gung Memorial HospitalAbstract 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.https://doi.org/10.1186/s13075-022-02933-4GoutHypertensionMendelian randomisation |
| spellingShingle | Benjamin Lai Huang-Ping Yu Yu-Jing Chang Liang-Chin Wang Che-Kai Chen Weiya Zhang Michael Doherty Shang-Hung Chang Jun-Te Hsu Kuang-Hui Yu Chang-Fu Kuo Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures Arthritis Research & Therapy Gout Hypertension Mendelian randomisation |
| 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 | Gout Hypertension Mendelian randomisation |
| url | https://doi.org/10.1186/s13075-022-02933-4 |
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