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

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 relations...

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Autores principales: Wei, Zhengxiao, Xiong, Qingqing, Huang, Dan, Wu, Zhangjun, Chen, Zhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10559484/
https://www.ncbi.nlm.nih.gov/pubmed/37805474
http://dx.doi.org/10.1186/s12879-023-08662-6
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author Wei, Zhengxiao
Xiong, Qingqing
Huang, Dan
Wu, Zhangjun
Chen, Zhu
author_facet Wei, Zhengxiao
Xiong, Qingqing
Huang, Dan
Wu, Zhangjun
Chen, Zhu
author_sort Wei, Zhengxiao
collection PubMed
description 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] = 0.561, 95% confidence interval [CI]: 0.403–0.780, P < 0.001) and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (OR = 0.780, 95%CI: 0.689–0.883, P < 0.001) was causatively associated with a lower risk of sepsis, and genetically predicted phenylacetate (PA) (OR = 1.426, 95%CI: 1.152–1.765, P = 0.001) and cysteine (OR = 1.522, 95%CI: 1.170–1.980, P = 0.002) were associated with an increased risk of UTI. Ursodeoxycholate (UDCA) (OR = 0.906, 95%CI: 0.829–0.990, P = 0.029) is a protective factor against pneumonia. Two unknown metabolites, X-12407 (OR = 1.294, 95%CI: 1.131–1.481, P < 0.001), and X-12847 (OR = 1.344, 95%CI: 1.152–1.568, P < 0.001), were also identified as independent risk factors for sepsis. CONCLUSIONS: In this MR study, we demonstrated a causal relationship between blood metabolites and the risk of developing sepsis, pneumonia, and UTI. However, there was no evidence of a causal connection between blood metabolites and the risk of URTI or SSTI, indicating a need for larger-scale studies to further investigate susceptibility to certain infection phenotypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08662-6.
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spelling pubmed-105594842023-10-08 Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study Wei, Zhengxiao Xiong, Qingqing Huang, Dan Wu, Zhangjun Chen, Zhu BMC Infect Dis Research 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] = 0.561, 95% confidence interval [CI]: 0.403–0.780, P < 0.001) and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (OR = 0.780, 95%CI: 0.689–0.883, P < 0.001) was causatively associated with a lower risk of sepsis, and genetically predicted phenylacetate (PA) (OR = 1.426, 95%CI: 1.152–1.765, P = 0.001) and cysteine (OR = 1.522, 95%CI: 1.170–1.980, P = 0.002) were associated with an increased risk of UTI. Ursodeoxycholate (UDCA) (OR = 0.906, 95%CI: 0.829–0.990, P = 0.029) is a protective factor against pneumonia. Two unknown metabolites, X-12407 (OR = 1.294, 95%CI: 1.131–1.481, P < 0.001), and X-12847 (OR = 1.344, 95%CI: 1.152–1.568, P < 0.001), were also identified as independent risk factors for sepsis. CONCLUSIONS: In this MR study, we demonstrated a causal relationship between blood metabolites and the risk of developing sepsis, pneumonia, and UTI. However, there was no evidence of a causal connection between blood metabolites and the risk of URTI or SSTI, indicating a need for larger-scale studies to further investigate susceptibility to certain infection phenotypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08662-6. BioMed Central 2023-10-07 /pmc/articles/PMC10559484/ /pubmed/37805474 http://dx.doi.org/10.1186/s12879-023-08662-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wei, Zhengxiao
Xiong, Qingqing
Huang, Dan
Wu, Zhangjun
Chen, Zhu
Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title_full Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title_fullStr Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title_full_unstemmed Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title_short Causal relationship between blood metabolites and risk of five infections: a Mendelian randomization study
title_sort causal relationship between blood metabolites and risk of five infections: a mendelian randomization study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10559484/
https://www.ncbi.nlm.nih.gov/pubmed/37805474
http://dx.doi.org/10.1186/s12879-023-08662-6
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