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. 2025 Apr 11;104(15):e42102.
doi: 10.1097/MD.0000000000042102.

The causal relationship between smoking, alcohol consumption, and sepsis: A 2-sample mendelian randomized study

Yonghan Luo  1   2 , Xiaotao Yang  1 , Yanchun Wang  1
Affiliations

The causal relationship between smoking, alcohol consumption, and sepsis: A 2-sample mendelian randomized study

Yonghan Luo et al. Medicine (Baltimore). .

Abstract

A Mendelian randomization (MR) study was used to explore whether there is a causal relationship between smoking, alcohol consumption, and sepsis. Genome-wide association studies data on sepsis, alcohol consumption, and 3 smoking behaviors including smoking initiation, age of initiation, and cigarettes per day were extracted from public databases. The inverse variance weighting (IVW), weighted median, and MR-Egger regression method were used to analyze the causal association between smoking, alcohol consumption, and sepsis. Forest plots of the causal relationship between smoking, alcohol consumption, and sepsis were plotted. The MR Analysis based mainly on IVW showed a causal relationship between cigarettes per day and sepsis (OR = 1.24, 95% CI = 1.11-1.37, P = .000). Heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis. MR Analysis showed that there was no causal association between sepsis and smoking initiation, age of initiation, and alcohol consumption. There is a positive causal effect between cigarettes per day and the risk of sepsis. However, there was insufficient evidence for a causal relationship between sepsis and smoking initiation, age of initiation, and alcohol consumption.

Keywords: Mendelian randomization; alcohol consumption; sepsis; smoking.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Flow chart of 2-sample MR. Assumption 1: the genetic variants proposed as IV should be robustly associated with the exposure. Assumption 2: IV should not be associated with potential confounders. Assumption 3: IV should affect the risk of the outcome merely through the risk factor, not via alternative pathways. IV = instrumental variables, MR = Mendelian randomization.
Figure 2.
Figure 2.
Forest plot of causal relationship between smoking, alcohol consumption, and sepsis.
Figure 3.
Figure 3.
Funnel plot of SNPs associated with cigarettes per day and their risk of sepsis. SNPs = single nucleotide polymorphisms.
Figure 4.
Figure 4.
Scatter plot of SNPs associated with cigarettes per day and their risk of sepsis. SNPs = single nucleotide polymorphisms.
Figure 5.
Figure 5.
The leave-one-out analysis for cigarettes per day on sepsis.
See this image and copyright information in PMC

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