Gao Yan, Wang Yiguo, Su Jinwen, Zhang Chunxia, Zhang Qiming, Chen Zhi
ICU, Tuberculosis Department 8th Medical Center of Chinese PLA General Hospital Tuberculosis Research Institute Beijing China.
Experimental Research Center China Academy of Chinese Medical Sciences Beijing China.
Health Sci Rep. 2025 May 29;8(6):e70875. doi: 10.1002/hsr2.70875. eCollection 2025 Jun.
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.
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.
The inverse variance weighting analyses indicated that ENMD significantly increased the risk of PTB (OR = 1.41, 95% CI: 1.18-1.68, < 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, = 0.10), whereas high cholesterol (OR = 0.41, 95% CI: 0.22-0.79, < 0.05), BMI (OR = 0.78, 95% CI: 0.69-0.88, < 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, = 0.03). Sensitivity analyses confirmed the robustness of these findings.
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.
观察性研究经常报告内分泌、营养和代谢性疾病（ENMD）与肺结核（PTB）之间的共现情况。然而，它们之间的因果关系仍不明确。本研究的目的是使用孟德尔随机化分析来研究ENMD对PTB的因果效应。
我们从IEU OpenGWAS项目中获得了与ENMD、ENMD相关疾病和临床特征以及PTB相关的单核苷酸多态性。采用逆方差加权作为主要分析方法，并辅以加权中位数和MR-Egger回归来评估它们的因果关系。使用Cochran's Q检验和MR回归截距评估异质性和水平多效性。通过留一法敏感性分析和MR-PRESSO评估结果的稳健性。
逆方差加权分析表明，在去除异常值后，ENMD显著增加了PTB的风险（OR = 1.41，95% CI：1.18 - 1.68，P < 0.001）。有趣的是，在欧洲血统的遗传水平上，没有证据表明2型糖尿病会增加PTB的风险（OR = 1.05，95% CI：0.99 - 1.
