Exploring the bidirectional causal association between Sleep Apnea Syndrome and Depression: A Mendelian randomization study involving gut microbiota, serum metabolites, and inflammatory factors

Abstract

ObjectiveThis study aimed to investigate the potential causal association between Sleep Apnea Syndrome (SAS) and Depression, focusing on the roles of gut microbiota, serum metabolites, and inflammatory factors in these conditions. MethodsMendelian Randomization (MR) analysis was performed using data from genome-wide association studies to assess 211 types of gut microbiota, 1400 serum metabolites, and 91 inflammatory factors as potential contributing factors. Causal inference was conducted using the Inverse Variance Weighted (IVW) method, with additional robustness checks through Cochran's Q test, MR-Egger regression intercept test, MR-PRESSO global test, and leave-one-out analysis. ResultsThe MR analysis indicated a positive correlation between the risk of SAS and Depression (OR = 1.12, 95 % CI: 1.05–1.19, P < 0.001), with a reciprocal analysis showing a similar positive correlation between Depression and the risk of SAS (OR = 1.19, 95 % CI: 1.07–1.31, P = 0.001). Additionally, causal associations were identified between 15 types of gut microbiota, 36 serum metabolites, and 2 inflammatory factors with SAS, and between 11 types of gut microbiota, 23 serum metabolites, and 3 inflammatory factors with Depression (IVW, all P < 0.05). The robustness of these findings was confirmed through the MR-Egger regression intercept test and MR-PRESSO global test. ConclusionThis study provides epidemiological evidence of a bidirectional causal association between SAS and Depression, emphasizing the potential roles of gut microbiota, serum metabolites, and inflammatory factors in the pathogenesis of these disorders. These findings may inform the development of new therapeutic strategies.