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Updated: Mar 31, 2026

Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
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Identification of potential drug targets for delirium from genetic insights: A Mendelian randomization study

Yan-Na Geng1, Xu Dong1, Yuan Liu1

  • 1Intensive Care Unit, Hebei University of Chinese Medicine Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei Province, China.

Brain Research Bulletin
|March 29, 2026
PubMed

Insights

This study identified PSORS1C3 and POU5F1 as key genes influencing delirium risk using Mendelian randomization. These findings offer genetic targets for developing new delirium treatments.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Delirium is a common acute brain disorder with significant clinical impact.
  • Current pharmacological treatments for delirium are limited.
  • Genetic insights offer a promising avenue for discovering novel therapeutic targets.

Purpose of the Study:

  • To systematically screen druggable genes for potential causal roles in delirium susceptibility using Mendelian randomization (MR).
  • To prioritize candidate genes for future functional studies and drug repurposing efforts in delirium.

Main Methods:

  • Utilized Mendelian randomization (MR) to analyze associations between 5,883 druggable genes and delirium risk.
  • Applied summary-data-based MR (SMR) and HEIDI tests for further validation.
  • Conducted exploratory two-step MR mediation analysis to investigate potential biological pathways.

Main Results:

  • Identified 11 druggable genes with evidence of a causal role in delirium susceptibility.
  • PSORS1C3 showed significant genetic colocalization with delirium risk (PP.H4 = 0.746).
  • Exploratory analysis suggested POU5F1 and PSORS1C3 may regulate white matter connectivity, potentially reducing delirium risk.

Conclusions:

  • PSORS1C3 and POU5F1 are prioritized as high-confidence candidate genes for delirium susceptibility.
  • This genetic evidence provides a foundation for future functional research and drug development for delirium.
  • Further validation of mediation findings in independent cohorts is warranted.
Keywords:
DeliriumDrug targetsGeneticsMendelian randomization

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