Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study
Abstract Background and Aims Observational studies frequently report co‐occurrence between endocrine, nutritional, and metabolic disease (ENMD) and pulmonary tuberculosis (PTB). However, the causal properties between them remain poorly defined. Our aim in this study was to investigate the causal eff...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/hsr2.70875 |
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| author | Yan Gao Yiguo Wang Jinwen Su Chunxia Zhang Qiming Zhang Zhi Chen |
| author_facet | Yan Gao Yiguo Wang Jinwen Su Chunxia Zhang Qiming Zhang Zhi Chen |
| author_sort | Yan Gao |
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| description | Abstract Background and Aims Observational studies frequently report co‐occurrence between endocrine, nutritional, and metabolic disease (ENMD) and pulmonary tuberculosis (PTB). However, the causal properties between them remain poorly defined. Our aim in this study was to investigate the causal effect of ENMD on PTB using Mendelian randomization analysis. Methods We obtained single nucleotide polymorphisms linked to ENMD, ENMD‐related diseases, and clinical features, as well as PTB, from the IEU OpenGWAS project. Inverse variance weighting was used as the primary analytical method, complemented by Weighted median and MR‐Egger regression to assess their causal relationship. Heterogeneity and horizontal pleiotropy were assessed using Cochran's Q test and MR regression intercepts. The robustness of the results is evaluated by sensitivity analysis leave‐one‐out and MR‐PRESSO. Results The inverse variance weighting analyses indicated that ENMD significantly increased the risk of PTB (OR = 1.41, 95% CI: 1.18–1.68, p < 0.001) after removing outliers. Interestingly, at the genetic level of European ancestry, there is no evidence of increased risk of PTB with T2DM (OR = 1.05, 95% CI: 0.99–1.12, p = 0.10), whereas high cholesterol (OR = 0.41, 95% CI: 0.22–0.79, p < 0.05), BMI (OR = 0.78, 95% CI: 0.69–0.88, p < 0.001) was negatively correlated with the risk of PTB, and LDL‐c showed a weak inverse correlation with PTB (OR = 0.90, 95% CI: 0.81–0.99, p = 0.03). Sensitivity analyses confirmed the robustness of these findings. Conclusion This MR study provides novel genetic evidence that ENMD significantly elevates PTB risk. Notably, high cholesterol, BMI, and LDL‐c exhibit protective effects against PTB at the genetic level in European ancestry, while T2DM shows no causal association. These findings highlight the complex role of metabolic factors in tuberculosis susceptibility and suggest potential biological mechanisms linking metabolic dysregulation to PTB pathogenesis. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Health Science Reports |
| spelling | doaj-art-eb6d821614b84053a54eccf55186022b2025-08-20T02:35:26ZengWileyHealth Science Reports2398-88352025-06-0186n/an/a10.1002/hsr2.70875Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization StudyYan Gao0Yiguo Wang1Jinwen Su2Chunxia Zhang3Qiming Zhang4Zhi Chen5ICU, Tuberculosis Department 8th Medical Center of Chinese PLA General Hospital Tuberculosis Research Institute Beijing ChinaExperimental Research Center China Academy of Chinese Medical Sciences Beijing ChinaICU, Tuberculosis Department 8th Medical Center of Chinese PLA General Hospital Tuberculosis Research Institute Beijing ChinaICU, Tuberculosis Department 8th Medical Center of Chinese PLA General Hospital Tuberculosis Research Institute Beijing ChinaExperimental Research Center China Academy of Chinese Medical Sciences Beijing ChinaICU, Tuberculosis Department 8th Medical Center of Chinese PLA General Hospital Tuberculosis Research Institute Beijing ChinaAbstract Background and Aims Observational studies frequently report co‐occurrence between endocrine, nutritional, and metabolic disease (ENMD) and pulmonary tuberculosis (PTB). However, the causal properties between them remain poorly defined. Our aim in this study was to investigate the causal effect of ENMD on PTB using Mendelian randomization analysis. Methods We obtained single nucleotide polymorphisms linked to ENMD, ENMD‐related diseases, and clinical features, as well as PTB, from the IEU OpenGWAS project. Inverse variance weighting was used as the primary analytical method, complemented by Weighted median and MR‐Egger regression to assess their causal relationship. Heterogeneity and horizontal pleiotropy were assessed using Cochran's Q test and MR regression intercepts. The robustness of the results is evaluated by sensitivity analysis leave‐one‐out and MR‐PRESSO. Results The inverse variance weighting analyses indicated that ENMD significantly increased the risk of PTB (OR = 1.41, 95% CI: 1.18–1.68, p < 0.001) after removing outliers. Interestingly, at the genetic level of European ancestry, there is no evidence of increased risk of PTB with T2DM (OR = 1.05, 95% CI: 0.99–1.12, p = 0.10), whereas high cholesterol (OR = 0.41, 95% CI: 0.22–0.79, p < 0.05), BMI (OR = 0.78, 95% CI: 0.69–0.88, p < 0.001) was negatively correlated with the risk of PTB, and LDL‐c showed a weak inverse correlation with PTB (OR = 0.90, 95% CI: 0.81–0.99, p = 0.03). Sensitivity analyses confirmed the robustness of these findings. Conclusion This MR study provides novel genetic evidence that ENMD significantly elevates PTB risk. Notably, high cholesterol, BMI, and LDL‐c exhibit protective effects against PTB at the genetic level in European ancestry, while T2DM shows no causal association. These findings highlight the complex role of metabolic factors in tuberculosis susceptibility and suggest potential biological mechanisms linking metabolic dysregulation to PTB pathogenesis.https://doi.org/10.1002/hsr2.70875endocrineEuropean ancestryMendelian randomizationmetabolic diseasenutritionalpulmonary tuberculosis |
| spellingShingle | Yan Gao Yiguo Wang Jinwen Su Chunxia Zhang Qiming Zhang Zhi Chen Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study Health Science Reports endocrine European ancestry Mendelian randomization metabolic disease nutritional pulmonary tuberculosis |
| title | Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study |
| title_full | Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study |
| title_fullStr | Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study |
| title_full_unstemmed | Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study |
| title_short | Assessing Causality Between Endocrine, Nutritional, and Metabolic Disease and Pulmonary Tuberculosis: A Mendelian Randomization Study |
| title_sort | assessing causality between endocrine nutritional and metabolic disease and pulmonary tuberculosis a mendelian randomization study |
| topic | endocrine European ancestry Mendelian randomization metabolic disease nutritional pulmonary tuberculosis |
| url | https://doi.org/10.1002/hsr2.70875 |
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