Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis
Background Hyperuricemia and hypertension are prevalent chronic diseases that often co-occur. While numerous observational studies suggest an association between serum uric acid (SUA) levels and hypertension, the causal nature of this relationship remains unresolved due to confounding and reverse ca...
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Taylor & Francis Group
2025-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2025.2496514 |
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| author | Jiayue Xu Jiajing Zhao Jiaming Gu Wenjian Wang Jingxian Chen |
| author_facet | Jiayue Xu Jiajing Zhao Jiaming Gu Wenjian Wang Jingxian Chen |
| author_sort | Jiayue Xu |
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| description | Background Hyperuricemia and hypertension are prevalent chronic diseases that often co-occur. While numerous observational studies suggest an association between serum uric acid (SUA) levels and hypertension, the causal nature of this relationship remains unresolved due to confounding and reverse causation. This study systematically investigates the causal association between SUA levels and hypertension risk using Mendelian randomization (MR) methodologies.Methods We utilized single nucleotide polymorphisms (SNPs) identified in large-scale genome-wide association studies (GWAS) of European populations as genetic instruments for SUA levels. MR, a genetic epidemiology technique, uses genetic variations as proxies to mimic a randomized controlled trial and minimizing biases from confounding and reverse causation. Systolic and diastolic blood pressure (SBP and DBP) were the primary outcomes of interest. A two-sample MR analysis was conducted to assess the causal relationships, complemented by sensitivity analyses (weighted median, weighted mode, MR-Egger) to ensure result robustness. Findings are expressed as odds ratios (ORs) with 95% confidence intervals (Cis) per one standard deviation (SD) increase in SUA levels.Results Our MR analysis identified a significant causal effect of SUA levels on hypertension risk. Specifically, genetically predicted SUA levels were positively associated with SBP (β = 0.136 [0.035–0.238], p < .05) and DBP (β = 0.108 [0.007–0.209], p < .05).Conversely, reverse MR analysis revealed no significant causal effect of SBP (b = 0.058 [ − 9.52E-05-0.116],p = .0504] or DBP (β = 0.016 [ − 0.028–0.059], p > .05] on SUA levels, confirming the unidirectional nature of this association.Conclusion This study provides compelling evidence from MR supporting a unidirectional causal link between SUA levels and increased hypertension risk. Unlike prior observational studies, our genetic approach effectively mitigates confounding and reverse causation, offering novel insights into the etiology of hypertension. These findings highlight the clinical importance of managing SUA levels to mitigate hypertension risk. Further research, including randomized controlled trials, is needed to confirm these findings and explore potential therapeutic interventions targeting SUA. |
| format | Article |
| id | doaj-art-d0a814062c0649a588d4b5b7abc23fce |
| institution | OA Journals |
| issn | 1064-1963 1525-6006 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Clinical and Experimental Hypertension |
| spelling | doaj-art-d0a814062c0649a588d4b5b7abc23fce2025-08-20T01:48:57ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062025-12-0147110.1080/10641963.2025.2496514Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysisJiayue Xu0Jiajing Zhao1Jiaming Gu2Wenjian Wang3Jingxian Chen4Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, ChinaDepartment of Internal Medicine of Chinese Medicine, Shanghai Putuo Hospital of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Putuo People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Fudan University Affiliated Huashan Hospital, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, ChinaBackground Hyperuricemia and hypertension are prevalent chronic diseases that often co-occur. While numerous observational studies suggest an association between serum uric acid (SUA) levels and hypertension, the causal nature of this relationship remains unresolved due to confounding and reverse causation. This study systematically investigates the causal association between SUA levels and hypertension risk using Mendelian randomization (MR) methodologies.Methods We utilized single nucleotide polymorphisms (SNPs) identified in large-scale genome-wide association studies (GWAS) of European populations as genetic instruments for SUA levels. MR, a genetic epidemiology technique, uses genetic variations as proxies to mimic a randomized controlled trial and minimizing biases from confounding and reverse causation. Systolic and diastolic blood pressure (SBP and DBP) were the primary outcomes of interest. A two-sample MR analysis was conducted to assess the causal relationships, complemented by sensitivity analyses (weighted median, weighted mode, MR-Egger) to ensure result robustness. Findings are expressed as odds ratios (ORs) with 95% confidence intervals (Cis) per one standard deviation (SD) increase in SUA levels.Results Our MR analysis identified a significant causal effect of SUA levels on hypertension risk. Specifically, genetically predicted SUA levels were positively associated with SBP (β = 0.136 [0.035–0.238], p < .05) and DBP (β = 0.108 [0.007–0.209], p < .05).Conversely, reverse MR analysis revealed no significant causal effect of SBP (b = 0.058 [ − 9.52E-05-0.116],p = .0504] or DBP (β = 0.016 [ − 0.028–0.059], p > .05] on SUA levels, confirming the unidirectional nature of this association.Conclusion This study provides compelling evidence from MR supporting a unidirectional causal link between SUA levels and increased hypertension risk. Unlike prior observational studies, our genetic approach effectively mitigates confounding and reverse causation, offering novel insights into the etiology of hypertension. These findings highlight the clinical importance of managing SUA levels to mitigate hypertension risk. Further research, including randomized controlled trials, is needed to confirm these findings and explore potential therapeutic interventions targeting SUA.https://www.tandfonline.com/doi/10.1080/10641963.2025.2496514Serum uric acidhypertension riskMendelian randomizationcausal relationshipgenetic epidemiology |
| spellingShingle | Jiayue Xu Jiajing Zhao Jiaming Gu Wenjian Wang Jingxian Chen Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis Clinical and Experimental Hypertension Serum uric acid hypertension risk Mendelian randomization causal relationship genetic epidemiology |
| title | Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis |
| title_full | Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis |
| title_fullStr | Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis |
| title_full_unstemmed | Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis |
| title_short | Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis |
| title_sort | serum uric acid levels as a causal factor in hypertension insights from mendelian randomization analysis |
| topic | Serum uric acid hypertension risk Mendelian randomization causal relationship genetic epidemiology |
| url | https://www.tandfonline.com/doi/10.1080/10641963.2025.2496514 |
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