Background: Delirium is a frequent complication in hospitalized older adults post-surgery associated with adverse outcomes. Although anaesthesia is traditionally linked to increased delirium risk, the causal relationship remains uncertain. Methods: We conducted Mendelian randomization (MR) analyses using genome-wide association studies (GWAS) summary statistics to explore the causal effects of different anaesthesia types (general, regional, and local) on delirium risk. We employed the weighted median, MR-Egger, and MR-PRESSO methods for estimation and conducted sensitivity analyses to address pleiotropy and heterogeneity. Results: Genetically determined anaesthesia types showed no significant causal effect on delirium risk. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or significant heterogeneity. Conclusions: Mendelian randomization provides strong evidence against a causal link between genetically determined anaesthesia and increased delirium risk.

The authors have declared no competing interest.

This study was funded by Jilin Province Science and Technology Development Grant (grant Nos. 20210101452JC and YDZJ202301ZYTS096)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used (or will use) ONLY openly available human data that were originally located at: https://gwas.mrcieu.ac.uk/

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes