The Potential Association between Metabolic Disorders and Pulmonary Tuberculosis: A Mendelian Randomization Study

Abstract

Abstract Background: Metabolic disorders (MetD) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetD and pulmonary tuberculosis (PTB) remains poorly understood. Method: The summary statistics from genome-wide association studies (GWAS) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The fourteen metabolic factors were grouped into four categories: metabolic laboratory markers, blood pressure, anthropometric measurements, and metabolic diseases. The causal relationship between the metabolic factors and PTB was analyzed using two-sample MR. Additionally, the direct effects on the risk of PTB were investigated through Multivariate MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. Results: In two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. After adjusting for other laboratory markers, The combined odds (ORs) of PTB were 2.798(95%CI 1.484-5.274 P=0.001), 4.027(95%CI 1.140-14.219, P=0.03), 2.548(95%CI 1.269-5.115, P=0.009) for one SD increase in HDL-C, LDL, and TG, respectively. And TC (OR 0.131, 95%CI 0.028-0.607, P=0.009) was negatively correlated with PTB. We select BMI, DM, HDL-C, SBP, and TG as the diagnosis factors for metabolic syndrome. The combined ORs of PTB were 1.219 (95%CI 1.040-1.429 P=0.014) and 1.380(95%CI 1.035-1.841, P=0.028) for one SD increase in DM and HDL-C, respectively. Conclusions: This MR study demonstrates that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.