Causal Association Between Sepsis and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization...

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Observational studies suggest a link between sepsis and neurodegenerative diseases.
• Causality between sepsis and neurodegenerative diseases remains uncertain.

Purpose of the Study:

• To determine the causal association between sepsis and four neurodegenerative diseases using bidirectional two-sample Mendelian randomization (MR).
• Investigated Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Lewy body dementia.

Main Methods:

• Utilized genome-wide association study summary statistics.
• Employed inverse variance weighted (IVW) as the primary MR method, supplemented by MR-Egger, weighted median, and maximum likelihood methods.
• Conducted sensitivity analyses including heterogeneity (Cochrane's Q), horizontal pleiotropy (MR-Egger intercept, MR-PRESSO), and stability (leave-one-out) tests.

Main Results:

• Sepsis significantly elevates the risk of Alzheimer's disease (OR=1.11, p=0.025).
• No causal effect of sepsis was found for Parkinson's disease, ALS, or Lewy body dementia.
• Reverse MR analysis confirmed no causal effect of these neurodegenerative diseases on sepsis.

Conclusions:

• Sepsis is a causal risk factor for Alzheimer's disease.
• Findings clarify the unidirectional relationship between sepsis and specific neurodegenerative diseases.
• Provides insights for developing therapeutic strategies targeting sepsis-related complications.