Single-Cell and Mendelian Randomization Analyses Identify Key Genes Common to COVID-19 and Multiple Sclerosis

Area of Science:

• Immunology
• Genetics
• Computational Biology

Background:

• Multiple sclerosis (MS) and coronavirus disease 2019 (COVID-19) share similar inflammatory pathophysiology.
• B cells are central immune players in the pathogenesis of both MS and COVID-19.

Purpose of the Study:

• To elucidate the molecular mechanisms of B cell function in COVID-19 and MS.
• To identify common genetic risk and protective factors for both diseases.
• To explore potential therapeutic targets for comorbid COVID-19 and MS.

Main Methods:

• Integrated analysis of single-cell RNA sequencing (scRNA-seq), genome-wide association studies (GWAS), and expression quantitative trait locus (eQTL) data.
• Gene set enrichment analysis and pseudotime analysis of B cell trajectories.
• Differential gene expression analysis and Mendelian randomization.

Main Results:

• Increased B cell proportions observed in patients with COVID-19 and MS compared to healthy controls.
• Identified DR1, IKZF3, and RUVBL2 as risk factors, and ANAPC5 as a protective factor for both conditions.
• IKZF3 showed differential expression across B cell subsets, potentially linking inflammation and metabolism to disease onset and comorbidity.

Conclusions:

• IKZF3 may play a crucial role in the shared pathogenesis of COVID-19 and MS through immune inflammation and metabolic inhibition.
• The study highlights potential molecular interactions and clinical significance for understanding and treating these diseases concurrently.
• Identified key genes provide a foundation for developing targeted therapeutic strategies.