The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study
ABSTRACT 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 inve...
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2025-05-01
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| Online Access: | https://doi.org/10.1002/brb3.70494 |
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| author | Han Wu Ruilai Jiang Xiaocheng Huang Xiaogang Hu |
| author_facet | Han Wu Ruilai Jiang Xiaocheng Huang Xiaogang Hu |
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| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-ec2f239819ca417b8d853383cf4c8e5e |
| institution | OA Journals |
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| spelling | doaj-art-ec2f239819ca417b8d853383cf4c8e5e2025-08-20T02:29:19ZengWileyBrain and Behavior2162-32792025-05-01155n/an/a10.1002/brb3.70494The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization StudyHan Wu0Ruilai Jiang1Xiaocheng Huang2Xiaogang Hu3Department of Geriatrics the Second People's Hospital of Lishui Lishui ChinaZhejiang Chinese Medical University Hangzhou ChinaDepartment of Geriatrics the Second People's Hospital of Lishui Lishui ChinaDepartment of Geriatrics the Second People's Hospital of Lishui Lishui ChinaABSTRACT 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.https://doi.org/10.1002/brb3.70494deliriumglial cell‐derived neurotrophic factorMendelian randomizationneurotrophic factors |
| spellingShingle | Han Wu Ruilai Jiang Xiaocheng Huang Xiaogang Hu The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study Brain and Behavior delirium glial cell‐derived neurotrophic factor Mendelian randomization neurotrophic factors |
| title | The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study |
| title_full | The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study |
| title_fullStr | The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study |
| title_full_unstemmed | The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study |
| title_short | The Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study |
| title_sort | causal relationship between neurotrophic factors and delirium a mendelian randomization study |
| topic | delirium glial cell‐derived neurotrophic factor Mendelian randomization neurotrophic factors |
| url | https://doi.org/10.1002/brb3.70494 |
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