Postoperative delirium following major surgery was investigated for its genetic architecture using a case-control GWAS in the UK Biobank (1,016 cases; 139,148 controls), adjusting for age, sex, genotyping chip, and the first 10 principal components. The study identified seven SNPs mapping to four genes (APOE, TOMM40, APOC1, PVRL2), with two SNPs retaining significance after removing individuals with pre-existing dementia and five after excluding those with subsequent dementia.
The leading variant was rs429358, a missense change in APOE. Genetic correlation and polygenic risk score analyses suggested a shared genetic basis between postoperative delirium and both delirium of all causes and Alzheimer's disease, with a notable correlation to Alzheimer's disease (rho ≈ 0.68; 95% CI roughly 0.46–0.81).
The APOE ε4 isoform exhibited a dose-dependent increase in risk for postoperative delirium (odds ratios: 1 copy ≈ 1.75; 2 copies ≈ 4.19). The results imply genetic variants, particularly in APOE, contribute to delirium risk and indicate overlap with Alzheimer’s disease liability.
Uncertainty remains regarding replication and clinical translation pending validation in independent cohorts.
PLOS Medicine published a clinical update in Research Highlights on 02 Mar 2026.
The item focuses on The genetic architecture of postoperative delirium after major surgery and its relationship with nonpostoperative neurocognitive conditions: A genome-wide association study.
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