Inflammatory biomarkers and delirium: a Mendelian randomization study

Area of Science:

• Genetics
• Immunology
• Neuroscience

Background:

• The relationship between inflammatory markers and delirium symptoms is debated.
• Observational studies show inconsistent associations.
• Causal links require robust investigation.

Purpose of the Study:

• To investigate the causal relationship between inflammatory biomarkers and delirium risk.
• To utilize Mendelian randomization to assess genetic associations.
• To explore potential bidirectional causality.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) was employed.
• Genetic instruments for 9 inflammatory biomarkers were identified from large GWAS.
• Summary statistics for delirium were obtained from the FinnGen consortium.

Main Results:

• Soluble IL-6 receptor alpha (sIL-6Rα) showed a potential association with decreased delirium risk at a stringent genome-wide significance level (P < 5e-8).
• This association became non-significant with a more liberal threshold (P < 5e-6).
• No significant causal effects were found for other tested inflammatory biomarkers (TNF-α, CRP, IL-1α, IL-1β, IL-2, IL-6, IL-8, soluble gp130) or reverse causation.

Conclusions:

• This MR analysis does not support a causal association between the investigated peripheral inflammatory biomarkers and delirium.
• Further research is necessary to elucidate the role of inflammatory factors in delirium pathogenesis.