Genome-wide Association Study of Postoperative Cognitive Dysfunction in Older Surgical Patients.

Rickenbacher, Marc; Reinbold, Céline S; Herms, Stefan; Hoffmann, Per; Cichon, Sven; Wueest, Alexandra S; Monsch, Andreas U; Steiner, Luzius A; Goettel, Nicolai

BACKGROUND Postoperative cognitive dysfunction (POCD) is a common neurocognitive disorder after surgery and anesthesia, particularly in elderly patients. Various studies have suggested genetic risk factors for POCD. The study aimed to detect genome-wide associations of POCD in older patients. METHODS In this prospective observational cohort study, participants aged 65 years and above completed a set of neuropsychological tests before, at 1 week, and 3 months after major noncardiac surgery. Test variables were converted into standard scores (z-scores) based on demographic characteristics. POCD was diagnosed if the decline was >1 SD in ≥2 of the 15 variables in the assessment battery. A genome-wide association study (GWAS) was performed to determine potential alleles that are linked to the POCD phenotype. In addition, candidate genes for POCD were identified in a literature search for further analysis. RESULTS Sixty-three patients with blood samples were included in the study. POCD was diagnosed in 47.6% of patients at 1 week and in 34.2% of patients at 3 months after surgery. Insufficient sample quality led to exclusion of 26 patients. In the remaining 37 patients, a GWAS was performed, but no association (P<5×10) with POCD was found. The subsequent gene set enrichment analysis of 34 candidate genes did not reveal any significant associations. CONCLUSION In this patient cohort, a GWAS did not reveal an association between specific genetic alleles and POCD at 1 week and 3 months after surgery. Future genetic analysis should focus on specific candidate genes for POCD.