Type 2 diabetes and glycemic traits are not causal factors of delirium: A two-sample mendelian randomization analysis

Abstract

This study aims to explore the genetic causal association between type 2 diabetes (T2D) and glycemic traits (fasting glucose [FG], fasting insulin [FI], and glycated hemoglobin [HbA1c]) on delirium using Mendelian randomization (MR). Genome-wide association studies (GWAS) summary data for T2D and glycemic traits were obtained from the IEU OpenGWAS database. GWAS summary data for delirium were obtained from the FinnGen Consortium. All the participants were of European ancestry. In addition, we used T2D, FG, FI, and HbA1c as exposures and delirium as outcomes. A random-effects variance-weighted model (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform MR analysis. In addition, MR-IVW and MR-Egger analyses were used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using MR-Egger regression and MR pleiotropy residual sum and outliers (MR-PRESSO). MR-PRESSO was also used to assess outlier single nucleotide polymorphisms (SNPs). The “leave one out” analysis was used to investigate whether the MR analysis results were influenced by a single SNP and evaluate the robustness of the results. In this study, we conducted a two-sample MR analysis, and there was no evidence of a genetic causal association between T2D and glycemic traits (T2D, FG, FI, and HbA1c) on delirium (all p > 0.05). The MR-IVW and MR-Egger tests showed no heterogeneity in our MR results (all p values >0.05). In addition, The MR-Egger and MR-PRESSO tests showed no horizontal pleiotropy in our MR results (all p > 0.05). The MR-PRESSO results also showed that there were no outliers during the MR analysis. In addition, the “leave one out” test did not find that the SNPs included in the analysis could affect the stability of the MR results. Therefore, our study did not support the causal effects of T2D and glycemic traits (FG, FI, and HbA1c) on delirium risk.