Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study

作者：Zhengxiao Wei, Qingqing Xiong, Dan Huang, Zhangjun Wu, Zhu Chen · 发表于：BMC Infectious Diseases · 年份：2023 · DOI：10.1186/s12879-023-08662-6 · 被引用次数：7 · 研究领域：Metabolomics and Mass Spectrometry Studies、Genetic Associations and Epidemiology、Gut microbiota and health

OBJECTIVE: Infectious diseases continue to pose a significant threat in the field of global public health, and our understanding of their metabolic pathogenesis remains limited. However, the advent of genome-wide association studies (GWAS) offers an unprecedented opportunity to unravel the relationship between metabolites and infections. METHODS: Univariable and multivariable Mendelian randomization (MR) was commandeered to elucidate the causal relationship between blood metabolism and five high-frequency infection phenotypes: sepsis, pneumonia, upper respiratory tract infections (URTI), urinary tract infections (UTI), and skin and subcutaneous tissue infection (SSTI). GWAS data for infections were derived from UK Biobank and the FinnGen consortium. The primary analysis was conducted using the inverse variance weighted method on the UK Biobank data, along with a series of sensitivity analyses. Subsequently, replication and meta-analysis were performed on the FinnGen consortium data. RESULTS: After primary analysis and a series of sensitivity analyses, 17 metabolites were identified from UK Biobank that have a causal relationship with five infections. Upon joint analysis with the FinGen cohort, 7 of these metabolites demonstrated consistent associations. Subsequently, we conducted a multivariable Mendelian randomization analysis to confirm the independent effects of these metabolites. Among known metabolites, genetically predicted 1-stearoylglycerol (1-SG) (odds ratio [OR] = 0...