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Deciphering genetic causality between plasma BDNF and 91 circulating inflammatory proteins through bidirectional

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This study used Mendelian randomization to investigate causal links between brain-derived neurotrophic factor (BDNF) and inflammation. Findings suggest BDNF influences certain inflammatory proteins, potentially impacting neurological diseases.

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Area of Science:

  • Neuroscience
  • Immunology
  • Genetics
  • Epidemiology

Background:

  • Previous research indicates associations between blood levels of brain-derived neurotrophic factor (BDNF) and inflammatory factors.
  • The causal relationship between BDNF and inflammation remains unclear, hindering understanding of inflammation-related neurological diseases.

Purpose of the Study:

  • To investigate the causal relationships between plasma BDNF levels and 91 circulating inflammatory proteins using Mendelian randomization (MR).
  • To elucidate the potential role of BDNF in the pathogenesis and progression of inflammation-related neurological diseases.

Main Methods:

  • A Mendelian randomization (MR) study design was employed.
  • Genome-wide association study (GWAS) data for plasma BDNF levels (N=3,301) and 91 inflammation proteins (N=14,824) from European participants were utilized.
  • Primary analysis used the inverse variance weighted (IVW) method, supported by MR-Egger, weighted median, and other methods; sensitivity analyses assessed heterogeneity, pleiotropy, and robustness.

Main Results:

  • Elevated plasma BDNF levels were genetically associated with decreased concentrations of 13 inflammatory proteins, including IL-33, IL-17A, and Beta-NGF.
  • The association between BDNF and IL-33 remained significant after FDR correction.
  • Reverse MR suggested positive causal effects of CCL23, CDCP1, and NRTN on BDNF levels, and negative associations with ADA, CST5, IL-13, IL-17A, and VEGF-A.

Conclusions:

  • Genetically determined plasma BDNF levels influence IL-33 and are possibly associated with 12 other circulating inflammatory proteins.
  • Eight inflammatory proteins show potential negative or protective roles concerning BDNF levels.
  • These findings provide insights into the pathogenesis of inflammation-related neurological diseases and highlight potential therapeutic targets.