Exploring the Causal Link Between Plasma Lipidome and Trigeminal Neuralgia Using Bidirectional Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Metabolomics

Background:

• Trigeminal neuralgia (TN) is a debilitating neurological disorder causing severe facial pain.
• The role of plasma lipids in TN pathogenesis is not well understood.
• Understanding lipid associations may reveal novel therapeutic targets for TN.

Purpose of the Study:

• To investigate the causal association between plasma lipidome and TN using a bidirectional two-sample Mendelian randomization (MR) approach.
• To identify specific lipid species that may influence TN risk.
• To explore potential therapeutic strategies for TN management based on lipid associations.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analysis.
• Utilized genome-wide association study (GWAS) summary statistics for plasma lipidome and TN.
• Employed inverse variance weighted (IVW) regression with sensitivity analyses (MR-Egger, MR-PRESSO) to ensure robustness and assess pleiotropy.

Main Results:

• Genetically predicted glycerophospholipids (GP) and glycerolipid family (GL) showed significant causal effects on TN risk.
• Specific lipids like phosphatidylinositol (PI), diacylglycerol, and triacylglycerol were associated with reduced TN risk.
• Certain phosphatidylcholine (PC) configurations demonstrated a bidirectional causal relationship with TN, with PC (18:0_18:2) being notable.

Conclusions:

• Established causal links between specific plasma lipidomes and TN risk.
• Identified protective lipid species that may reduce TN susceptibility.
• Revealed a bidirectional relationship for PC, suggesting it as a potential therapeutic target for TN management.