# Identifying depression’s genetic role as a precursor to sepsis and increased mortality risk: Comprehensive insights from mendelian randomization analysis

## TL;DR

This study finds a genetic link between depression and increased sepsis risk, but not mortality from sepsis, suggesting depression management could help prevent sepsis.

## Contribution

The study provides novel evidence of a potential causal relationship between depression and sepsis using Mendelian randomization.

## Key findings

- Depression is causally linked to increased sepsis risk (OR = 1.246).
- No causal link was found between depression and sepsis-induced mortality.
- Sensitivity analyses confirmed the robustness of the sepsis risk findings.

## Abstract

Previous retrospective studies have shown a correlation between depression and increased risk of infections, including a moderate rise in sepsis likelihood associated with severe depression and anxiety. To investigate the potential causal links between depression, sepsis, and mortality risks, while considering confounding factors, we employed a Mendelian randomization (MR) approach.

In this two-sample Mendelian randomization study, we analyzed data from a large-scale genome-wide association study on depression, involving 807,553 European individuals (246,363 cases, 561,190 controls). We extracted SNP associations with sepsis and 28-day mortality from UK Biobank GWAS outcomes. The correlation analysis primarily employed the inverse-variance weighted method, supplemented by sensitivity analyses for heterogeneity and pleiotropy assessment.

Our analysis revealed a potential causal link between depression and an increased risk of sepsis (OR = 1.246, 95% CI: 1.076–1.442, P = 0.003), but no causal association was found with sepsis-induced mortality risk (OR = 1.274, 95% CI: 0.891–1.823, P = 0.184). Sensitivity analyses confirmed the robustness of these findings.

We identified a potential causal association between depression and heightened sepsis risk, while no link was found with sepsis-induced mortality. These findings suggest that effective management of depression could be important in preventing sepsis.