Abstract
Previous observational inquiries have revealed a correlation between depression and infectious maladies. This study seeks to elucidate the causal linkages between depression, specifically Major Depressive Disorder (MDD), and infectious diseases. Nevertheless, the causative nature of the association between MDD and infectious diseases remains elusive. Two-sample Mendelian Randomization (MR) analyses was executed utilizing single nucleotide polymorphisms (SNPs) significantly connected with MDD and infectious diseases as instrumental variables (IVs). A series of sensitivity analyses were subsequently conducted. Genetic variants linked to MDD were employed as instrumental variables sourced from a genome-wide meta-analyses comprising 500,199 individuals. Summary-level data on five infectious diseases, including candidiasis, pneumonia, skin and soft tissue infections (SSTI), upper respiratory tract infections (URTI), and urinary tract infections (UTI), were acquired from the UK Biobank and FinnGen study. Our findings evinced that genetically predicted MDD exhibited a heightened risk of candidiasis (OR = 1.52, 95% CI 1.06-2.17; P = 2.38E-02), pneumonia (OR = 1.14, 95% CI 1.01-1.29; P = 3.16E-02), URTI (OR = 1.23, 95% CI 1.12-1.36; P = 3.71E-05), and UTI (OR = 1.26, 95% CI 1.12-1.42; P = 8.90E-05). Additionally, we identified bidirectional causal relationships between UTI and MDD. The associations between MDD and the risk of URTI and UTI remained consistent in multivariable MR analyses, accounting for genetically predicted smoking and body mass index. In conclusion, this investigation ascertained a causal connection between MDD and the susceptibility to infectious diseases, particularly URTI and UTI.