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

Abstract

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.