Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation

Wei Wang; Runshi Gao; Xiaoming Yan; Wei Shu; Xi Zhang; Wenjie Zhang; Lan Zhang

doi:10.1016/j.heliyon.2024.e30415

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation

Heliyon. 2024 Apr 26;10(9):e30415. doi: 10.1016/j.heliyon.2024.e30415. eCollection 2024 May 15.

Authors

Wei Wang¹, Runshi Gao², Xiaoming Yan², Wei Shu², Xi Zhang², Wenjie Zhang², Lan Zhang¹

Affiliations

¹ Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China.
² Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Abstract

Background: Altered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders.

Objective: To investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study.

Methods: We selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders).

Results: We observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774-0.958, P = 0.006, P_FDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880-0.976, P = 0.004, P_FDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874-0.986, P = 0.016, P_FDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964-0.999, P = 0.041, P_FDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81-0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95 % CI: 0.90-0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95 % CI: 0.89-0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes.

Conclusions: Our study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

Keywords: BDNF; Mendelian randomisation; Neurological disorders; Risk factors.