Association of air pollution, lifestyle factors, and metabolic syndrome: a Mendelian randomization study

Background: Uncertainty existed regarding the causal associations between air pollution, lifestyle factors, and the risk of metabolic syndrome (MetS). Objective： We examined this using two-sample univariable Mendelian randomization (MR) and multivariable MR analysis. Methods: Independent genetic variants linked to 4 air pollutants and 10 lifestyle factors were chosen as instrumental variables from genome-wide association studies. The FinnGen, UK Biobank studies, and other large consortia provided genetic connections with MetS and its components. Furthermore, mediation analysis was performed to assess the proportions mediated by inflammatory markers, including C-reactive protein (CRP) and 41 circulating cytokines. Results: We found particulate matter with a diameter < 2.5μm (PM _2.5 ) [ OR: 1.30(1.17,1.46), p < 0.001], nitrogen oxides (NO _x ) [ OR:1.13(1.03,1.23), p = 0.007], leisure screen time: (LST) [ OR: 1.28(1.24,1.32), p < 0.001], smoking initiation [ OR: 1.19(1.15,1.23), p <0.001] and coffee intake [ OR: 1.33(1.22,1.45), p < 0.001] with increased the risk of MetS, while Moderate-to-vigorous physical activity (MVPA) exhibited protective effects [ OR: 0.73(0.69,0.78), p <0.001]. Furthermore, there were associations between drinks per week, relative carbohydrate intake, relative fat intake, and sedentary commuting and the components of Mets. The above P values were all <0.05. Mediation analysis revealed that CRP mediated 3.93-36.63% of effects from PM _2.5 , NO _x , LST, MVPA, smoking initiation, drinks per week, and relative carbohydrate intake on MetS or its components. Conclusions: This study identified 2 air pollutants and 8 lifestyle factors might have a causal relationship with MetS or its components, with CRP potentially mediating this relationship.