The relationship between major depression and delirium: A two-sample Mendelian randomization analysis

Background: Major depression (MD) is a well-recognized risk factor for delirium. However, observational studies cannot provide direct evidence of causality between MD and delirium. Methods: This study explored the genetic causal association between MD and delirium using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for MD were obtained from the UK Biobank. GWAS summary data for delirium were obtained from the FinnGen Consortium. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform the MR analysis. In addition, the Cochrane's Q test was used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. Leave-one-out analysis was used to investigate the sensitivity of this association. Results: The IVW method showed that MD was an independent risk factor for delirium (P = 0.013). Horizontal pleiotropy was unlikely to bias causality (P > 0.05), and no evidence of heterogeneity was found between the genetic variants (P > 0.05). Finally, a leave-one-out test showed that this association was stable and robust. Limitations: All participants included in the GWAS were of European ancestry. Due to database limitations, the MR analysis did not conduct stratified analyses for different countries, ethnicities, or age groups. Conclusion: We conducted a two-sample MR analysis and found the evidence of genetic causal association between MD and delirium.