Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study

Abstract. Background. Energy metabolism disorders contribute to the development of sepsis. Carnitine is essential for fatty acid metabolism and energy production. Therefore, we aimed to explore whether there is a causal relationship between carnitine levels and sepsis. Methods. Two-sample Mendelian...

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Main Authors: Qingju Zhang, Xilong Liu, Qi Shen, Xingfang Wang, Jiaojiao Pang, Yuguo Chen
Format: Article
Language:English
Published: Wolters Kluwer Health/LWW 2024-12-01
Series:Emergency and Critical Care Medicine
Online Access:http://journals.lww.com/10.1097/EC9.0000000000000120
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author Qingju Zhang
Xilong Liu
Qi Shen
Xingfang Wang
Jiaojiao Pang
Yuguo Chen
author_facet Qingju Zhang
Xilong Liu
Qi Shen
Xingfang Wang
Jiaojiao Pang
Yuguo Chen
author_sort Qingju Zhang
collection DOAJ
description Abstract. Background. Energy metabolism disorders contribute to the development of sepsis. Carnitine is essential for fatty acid metabolism and energy production. Therefore, we aimed to explore whether there is a causal relationship between carnitine levels and sepsis. Methods. Two-sample Mendelian randomization (MR) analysis was performed. The single nucleotide polymorphisms (SNPs) of carnitine from the genome-wide association (GWAS) study were used as exposure instrumental variables, and the susceptibility and severity of sepsis in the UK Biobank were used as outcomes. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to evaluate the causal relationship between exposure and outcomes. Heterogeneity was assessed using IVW and MR-Egger’s and Cochran’s Q tests, and pleiotropy was tested using the MR-Egger intercept and MR-PRESSO. Results. Using the IVW method, a one-standard-deviation increase in genetically determined carnitine levels was found to be associated with increased susceptibility to sepsis in populations under 75 years of age (odds ratio [OR]: 2.696; 95% confidence interval [CI]: 1.127–6.452; P = 0.026) and increased severity of sepsis (OR: 22.31; 95% CI: 1.769–281.282; P = 0.016). Sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy; therefore, the results indicated robustness. Conclusion. Genetic susceptibility to increased carnitine levels in the blood may increase the susceptibility and severity of sepsis. Therefore, interventions at an early stage in patients with high carnitine levels may reduce the risk of developing sepsis.
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spelling doaj-art-731950e787cd4ed9aed57bd2e7607c602025-08-20T02:09:07ZengWolters Kluwer Health/LWWEmergency and Critical Care Medicine2097-06172693-860X2024-12-014414915410.1097/EC9.0000000000000120202412000-00003Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization studyQingju Zhang0Xilong Liu1Qi Shen2Xingfang Wang3Jiaojiao Pang4Yuguo Chen5a Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, Chinaa Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, Chinaa Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, Chinaa Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, Chinaa Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, Chinaa Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaAbstract. Background. Energy metabolism disorders contribute to the development of sepsis. Carnitine is essential for fatty acid metabolism and energy production. Therefore, we aimed to explore whether there is a causal relationship between carnitine levels and sepsis. Methods. Two-sample Mendelian randomization (MR) analysis was performed. The single nucleotide polymorphisms (SNPs) of carnitine from the genome-wide association (GWAS) study were used as exposure instrumental variables, and the susceptibility and severity of sepsis in the UK Biobank were used as outcomes. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to evaluate the causal relationship between exposure and outcomes. Heterogeneity was assessed using IVW and MR-Egger’s and Cochran’s Q tests, and pleiotropy was tested using the MR-Egger intercept and MR-PRESSO. Results. Using the IVW method, a one-standard-deviation increase in genetically determined carnitine levels was found to be associated with increased susceptibility to sepsis in populations under 75 years of age (odds ratio [OR]: 2.696; 95% confidence interval [CI]: 1.127–6.452; P = 0.026) and increased severity of sepsis (OR: 22.31; 95% CI: 1.769–281.282; P = 0.016). Sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy; therefore, the results indicated robustness. Conclusion. Genetic susceptibility to increased carnitine levels in the blood may increase the susceptibility and severity of sepsis. Therefore, interventions at an early stage in patients with high carnitine levels may reduce the risk of developing sepsis.http://journals.lww.com/10.1097/EC9.0000000000000120
spellingShingle Qingju Zhang
Xilong Liu
Qi Shen
Xingfang Wang
Jiaojiao Pang
Yuguo Chen
Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
Emergency and Critical Care Medicine
title Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
title_full Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
title_fullStr Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
title_full_unstemmed Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
title_short Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study
title_sort carnitine is causally associated with susceptibility and severity of sepsis a mendelian randomization study
url http://journals.lww.com/10.1097/EC9.0000000000000120
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