Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Transl Psychiatry. 2024 Jun 8;14(1):245. doi: 10.1038/s41398-024-02950-8.
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.
先前的观察性研究表明,抑郁与传染性疾病之间存在关联。本研究旨在阐明抑郁(特别是重度抑郁症)与传染病之间的因果关系。然而,抑郁与传染病之间的关联的因果性质仍难以捉摸。我们使用与抑郁显著相关的单核苷酸多态性(SNP)作为工具变量(IVs)进行了两样本孟德尔随机化(MR)分析。随后进行了一系列敏感性分析。使用来自包含 500,199 个人的全基因组荟萃分析的与 MDD 相关的遗传变异作为工具变量,分析了 MDD。从 UK Biobank 和 FinnGen 研究中获取了五种传染病(包括念珠菌病、肺炎、皮肤和软组织感染(SSTI)、上呼吸道感染(URTI)和尿路感染(UTI))的汇总水平数据。我们的研究结果表明,遗传预测的 MDD 与念珠菌病(OR=1.52,95%CI 1.06-2.17;P=2.38E-02)、肺炎(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)和 UTI(OR=1.26,95%CI 1.12-1.42;P=8.90E-05)的风险呈正相关。此外,我们还发现了 UTI 和 MDD 之间存在双向因果关系。在多变量 MR 分析中,考虑到遗传预测的吸烟和体重指数,MDD 与 URTI 和 UTI 风险之间的关联仍然一致。总之,本研究确定了 MDD 与传染病易感性之间的因果关系,特别是 URTI 和 UTI。