Causal relationship between mitochondrial function and delirium: a bidirectional two-sample Mendelian randomisation analysis.

Background: Previous studies have suggested a potential link between delirium and mitochondrial function. Consequently, this Mendelian randomisation (MR) study aimed to further investigate their causal relationship.

Methods: In this bidirectional MR study, the relationship between 73 proteins related to mitochondrial function and delirium, including delirium not induced by alcohol or other psychoactive substances (DEL) and delirium associated with alcohol withdrawal (AL-DEL). The random-effects inverse variance weighting (RE-IVW) method was used as the primary analytical method. Furthermore, multivariable MR (MVMR) analysis was performed to assess the impact of positive exposures and known risk factors for delirium. To ensure the reliability of our findings, heterogeneity and pleiotropy tests were conducted.

Results: The results of the RE-IVW method of MR analysis revealed that two proteins were positively associated with DEL (P < 0.05, odds ratio (OR) >1), whereas one protein was negatively associated with AL-DEL (P < 0.05, OR <1). In MVMR, ATP synthase subunit beta (ATP5F1B) was positively associated with DEL (P < 0.05, OR >1). Moreover, reverse MR analysis demonstrated that DEL was positively associated with three proteins (P < 0.05, OR >1) and negatively associated with two proteins (P < 0.05, OR <1). Finally, none of these associations displayed heterogeneity and horizontal pleiotropy (P > 0.05) or reverse causality.

Conclusions: This bidirectional, multivariable two-sample MR analysis identified a causal relationship between eight proteins related to mitochondrial function and delirium. These findings offer novel insights that could potentially influence early diagnosis, expand our understanding of the underlying mechanisms, and inform treatment strategies for delirium. Nevertheless, given the possibility of bias, these results should be interpreted with caution.