We examined the genetic architecture of postoperative delirium after major surgery and its relationship with related cognitive conditions (delirium of any type and Alzheimer's disease, including the APOE ε4 allele).<h4>Methods and findings</h4>A case-control GWAS was performed in the UK Biobank to identify genetic variants associated with postoperative delirium, adjusted for age, sex, genetic chip, and the first 10 principal components. The gene discussed is APOE; the disease is delirium.