Exploring causal correlations between plasma proteins and peripheral neuropathy: a Mendelian randomization.

Area of Science:

• Genetics
• Proteomics
• Neurology

Background:

• Peripheral neuropathy (PN) is a common neurological disorder.
• Circulating plasma proteins with causal genetic evidence represent key therapeutic targets.

Purpose of the Study:

• To identify plasma proteins causally associated with the risk of six common types of peripheral neuropathy.
• To discover novel therapeutic targets for PN through protein-mediated pathogenesis insights.

Main Methods:

• Employed two-sample Mendelian randomization (MR) and genome-wide association studies (GWAS) on plasma proteomes from 35,559 individuals.
• Utilized summary data for six common PN types from the FinnGen database.
• Conducted colocalization and drug-gene interaction analyses to identify causal protein-PN pairs and potential drug targets.

Main Results:

• Identified eight proteins (UBC12, SEM4C, IL23R, Prothrombin, CBS, Microglobulin, MATN4, COLEC12) with causal relationships to PN.
• UBC12 showed a protective effect for diabetic neuropathy (DP) and carpal tunnel syndrome (CTS); others were risk factors.
• Pathway enrichment analysis highlighted proteins involved in immune response and signaling pathways. Three genes (IL23R, F2, CBS) were identified as potential drug targets.

Conclusions:

• Mendelian randomization confirms causal links between genetically predicted PN risk and plasma protein abundance.
• Plasma proteins serve as valuable biomarkers for PN and potential targets for therapeutic interventions.