Brain and behavior · 2025
The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study.
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Wu Han, Jiang Ruilai, Huang Xiaocheng, Hu Xiaogang
Аннотация
BACKGROUND: Several observational studies have revealed that different neurotrophic factors (NTFs) are associated with delirium, yet the direction and magnitude of the causal association remain poorly understood. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between these factors and delirium.
METHODS: GWAS data for delirium were sourced from the FINN10 database; GWAS data for risk factors (protein kinase C-binding protein NELL1, neurotrophin-3, neurotrophin-4, brain-derived neurotrophic factor levels, nerve growth factor, ciliary neurotrophic factor, and glial cell-derived neurotrophic factor levels) were from the IEU Open GWAS. Inverse-variance weighted (IVW) was used as a primary analysis. MR-Egger, weighted median (WM), and weighted model were applied to validate the robustness of the results. The MR-Egger regression method was used to explore the presence of horizontal pleiotropy, and the MR pleiotropy residual sum, and outlier (MR-PRESSO) method was applied to detect potential outliers. Cochran's Q test assessed heterogeneity among instrumental variables (IVs). The leave-one-out (LOO) method was used to enhance the precision and veracity of our findings.
RESULTS: IVW analyses revealed no association between risk factors and delirium. MR Egger, WM, and the weighted mode approach further confirmed these data. MR-Egger regression analysis confirmed the absence of directional pleiotropy in our analysis. Heterogeneity and sensitivity analyses showed reliable results.
CONCLUSION: No association between other factors and delirium was identified; however, further research is needed to determine if these results apply to other races. Also, advances in molecular biology and epigenetics may shed light on this topic.
METHODS: GWAS data for delirium were sourced from the FINN10 database; GWAS data for risk factors (protein kinase C-binding protein NELL1, neurotrophin-3, neurotrophin-4, brain-derived neurotrophic factor levels, nerve growth factor, ciliary neurotrophic factor, and glial cell-derived neurotrophic factor levels) were from the IEU Open GWAS. Inverse-variance weighted (IVW) was used as a primary analysis. MR-Egger, weighted median (WM), and weighted model were applied to validate the robustness of the results. The MR-Egger regression method was used to explore the presence of horizontal pleiotropy, and the MR pleiotropy residual sum, and outlier (MR-PRESSO) method was applied to detect potential outliers. Cochran's Q test assessed heterogeneity among instrumental variables (IVs). The leave-one-out (LOO) method was used to enhance the precision and veracity of our findings.
RESULTS: IVW analyses revealed no association between risk factors and delirium. MR Egger, WM, and the weighted mode approach further confirmed these data. MR-Egger regression analysis confirmed the absence of directional pleiotropy in our analysis. Heterogeneity and sensitivity analyses showed reliable results.
CONCLUSION: No association between other factors and delirium was identified; however, further research is needed to determine if these results apply to other races. Also, advances in molecular biology and epigenetics may shed light on this topic.