What question did this study set out to answer?

The study aims to investigate the causal relationship between various neurotrophins and their effect on normal pressure hydrocephalus (NPH).

April 1, 2026Open Access

Causal Relationship Between Neurotrophins and Normal Pressure Hydrocephalus: Insights From a Bidirectional Two‐Sample Mendelian Randomization Study

Key Points

The study aims to investigate the causal relationship between various neurotrophins and their effect on normal pressure hydrocephalus (NPH).
Utilized two-sample Mendelian randomization (MR) study design
Analyzed comprehensive genome-wide association study (GWAS) data
Employed inverse-variance weighted (IVW) method and reverse causality analysis
Conducted sensitivity analyses with MR-Egger, MR-PRESSO, and others to validate findings
No statistical association found between neurotrophins and NPH in forward analysis
Reverse analysis indicated a negative causal association between NPH and CNTF with an odds ratio of 0.7963
Also found a negative association with GDNF with an odds ratio of 0.9576
Pleiotropy and outliers did not affect the results, validating robustness

Abstract

ABSTRACT Introduction Researchers have postulated a link between higher levels of brain‐derived neurotrophic factor (BDNF) and more favorable outcomes in patients with normal pressure hydrocephalus (NPH). However, there is no clear evidence regarding the causal association between neurotrophins and NPH. To delve deeper into this potential connection, scientists employed a rigorous method known as bidirectional Mendelian randomization (MR). This technique was utilized to explore the causal impact of various neurotrophins—such as BDNF, nerve growth factor (NGF), neurotrophin‐3 (NT‐3), NT‐4, ciliary neurotrophic factor (CNTF), and glial cell line‐derived neurotrophic factor (GDNF)—on the development or progression of NPH. Methods To investigate the causal relationship between five neurotrophin subtypes and NPH, we designed a two‐sample Mendelian randomization (MR) study using comprehensive genome‐wide association study (GWAS) data. Our primary approach involved the inverse‐variance weighted (IVW) method. We also conducted reverse causality analysis to ensure robustness. Furthermore, we implemented complementary methods like the weighted median (WM), weighted mode, and MR‐Egger to strengthen our findings. Sensitivity analyses, including MR‐Egger, MR‐PRESSO, leave‐one‐out, and Cochran's Q tests, were employed to validate results, explore heterogeneity and pleiotropy, and pinpoint potential biases. Results MR analysis of genetic prediction showed no statistical association of neurotrophins on NPH. However, a reverse analysis indicated a causal association between NPH and two neurotrophins: CNTF and GDNF. Specifically, individuals with NPH had a lower risk of CNTF (odds ratio: 0.7963, with a 95% confidence interval of 0.6537 to 0.9701, p = 0.0237) and a slightly reduced risk of GDNF (odds ratio: 0.9576, with a 95% confidence interval of 0.9226 to 0.9940, p = 0.0230). MR‐Egger regression showed that pleiotropy did not affect the analysis. In addition, MR‐PRESSO detected no outliers, and a leave‐one‐out analysis verified the robustness of the results. Conclusion NPH was negatively and causally associated with CNTF and GDNF. Additional research is crucial to uncover the underlying mechanisms and devise strategies, including nutritional guidelines, to prevent NPH.

Read Full Paperexternally

AI से पूछें

Bookmark

View Full Paper