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CAUSAL ASSOCIATION BETWEEN MEDICATION USE AND SEPSIS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.

Mingfen Sun1, Yi Chen2, Zhaoquan Jin1

  • 1Department of Emergency Medicine, The First People's Hospital of Changzhou, Changzhou, China.

Shock (Augusta, Ga.)
|March 18, 2025
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Genetically predicted diuretic use may increase sepsis risk. Evidence for other medications, including diabetes drugs and thyroid preparations, was inconclusive in this Mendelian randomization study.

Keywords:
Mendelian randomization analysisSepsiscausalitydiuretics

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Area of Science:

  • Pharmacogenomics
  • Infectious Disease Epidemiology

Background:

  • Sepsis is a life-threatening condition with significant morbidity and mortality.
  • Understanding the influence of prior medication use on sepsis risk is crucial for prevention and treatment strategies.

Purpose of the Study:

  • To investigate the potential causal relationship between genetically predicted medication use and the risk of developing sepsis.
  • To differentiate between potential associations and causal links using robust genetic methods.

Main Methods:

  • Employed a two-sample Mendelian randomization (MR) design using summary data from genome-wide association studies (GWAS).
  • Utilized Inverse Variance Weighted (IVW), weighted median, and MR-Egger regression methods for primary analysis.
  • Conducted sensitivity analyses including MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods to assess robustness and rule out pleiotropy.

Main Results:

  • Initial analysis suggested potential causal links between genetically predicted use of diuretics, drugs used in diabetes, thyroid preparations, and adrenergics with increased sepsis risk.
  • After adjusting for confounders, only genetically predicted diuretic use remained significantly associated with a higher risk of sepsis (OR = 1.17, P = 0.018).
  • Sensitivity analyses indicated minimal evidence of horizontal pleiotropy or heterogeneity influencing the association between diuretic use and sepsis.

Conclusions:

  • Prior use of diuretics may causally increase the risk of sepsis.
  • Evidence for a causal association between the use of other investigated medications (e.g., diabetes drugs, thyroid preparations) and sepsis risk was not supported by this study.
  • The findings highlight diuretics as a potential factor influencing sepsis risk, warranting further clinical investigation.