Study on the causal relationship between educational attainment and delirium: A two-sample Mendelian randomization study

Abstract

This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.

Keywords: Delirium; Educational attainment; Genetic level; Genome-wide association study (GWAS); Mendelian randomization.