The Role of HbA1c in Parkinson's Disease: An Integrative Analysis by Single-Cell, Bulk Transcriptome and Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Decreased glucose tolerance is linked to Parkinson's disease (PD) progression.
• The specific relationship between HbA1c and PD prognosis requires further investigation.

Purpose of the Study:

• To investigate the causal relationship between HbA1c and Parkinson's disease (PD).
• To identify potential diagnostic biomarkers for PD using genetic and gene expression data.

Main Methods:

• Mendelian Randomization (MR) analysis using Genome-Wide Association Study (GWAS) data for HbA1c and PD.
• Analysis of RNA-seq and single-cell RNA-seq data to identify differentially expressed genes (DEGs).
• Machine learning to refine candidate biomarkers and develop a PD diagnostic nomogram.

Main Results:

• HbA1c was found to be a causal risk factor for PD (OR=1.438, P=0.026).
• Five genes (FASN, MICAL3, TCIRG1, CDK10, MFSD1) were identified as potential diagnostic biomarkers for PD with high accuracy.
• Cellular communication analysis revealed interactions between excitatory/inhibitory neurons, oligodendrocyte precursor cells, and astrocytes.

Conclusions:

• Elevated HbA1c levels increase the risk of developing Parkinson's disease.
• The identified biomarkers offer potential for improved PD diagnosis and therapeutic targeting.