Evidence map›Paper›PMID 41913636›Full record

ArticleBrain and behavior2026

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

Tao Xu, Qiang Gan, Handong Wang, Haifeng Liu, Xiwen Huang

Abstract read
In one paragraph

Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Tao XuDepartment of Neurosurgery, Nanjing BenQ Medical Center, Nanjing, China.
Qiang GanDepartment of Neurosurgery, Nanjing BenQ Medical Center, Nanjing, China.
Handong WangDepartment of Neurosurgery, Nanjing BenQ Medical Center, Nanjing, China.
Haifeng LiuDepartment of Neurosurgery, Nanjing BenQ Medical Center, Nanjing, China.
Xiwen HuangDepartment of Neurosurgery, Nanjing BenQ Medical Center, Nanjing, China.

Funding

National Natural Science Foundation project 82271426
6 · The paper itself

Abstract

introductionResearchers 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.

methodsTo 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.

resultsMR 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.

conclusionNPH 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.

Indexed as

Hydrocephalus, Normal PressureNerve Growth FactorsCiliary Neurotrophic FactorGenome-Wide Association StudyHumansMendelian Randomization AnalysisCiliary Neurotrophic FactorNerve Growth Factorsciliary neurotrophic factor levels (CNTF)instrumental variablesMendelian randomizationneurotrophinsnormal pressure hydrocephalus (NPH)

Identifiers

PMID41913636
PMCPMC13112031

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.