AUTHOR=Li Jiajia , Yang Guixian , Liu Junnan , Li Guofeng , Zhou Huiling , He Yuan , Fei Xinru , Zhao Dongkai 

TITLE=Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare

JOURNAL=Frontiers in Genetics

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1385316

DOI=10.3389/fgene.2024.1385316

ISSN=1664-8021

ABSTRACT=There are considerable similarities between the pathophysiology of gout flare and the dysregulated inflammatory response in severe COVID-19 infection.Monocytes are the key immune cells involved in the pathogenesis of both diseases.Therefore, it is critical to elucidate the molecular basis of the function of monocytes in gout and COVID-19 in order to develop more effective therapeutic approaches.The single-cell RNA sequencing(scRNA-seq), large-scale genome-wide association studies (GWAS), and expression quantitative trait loci (eQTL) data of gout and severe COVID-19 were comprehensively analyzed. Cellular heterogeneity and intercellular communication were identified using the scRNA-seq datasets, and the monocyte-specific differentially expressed genes (DEGs) between COVID-19, gout and normal subjects were screened. In addition, the correlation of the DEGs with severe COVID-19 and gout flare was analyzed through GWAS statistics and eQTL data.The scRNA-seq analysis exhibited that the proportion of classical monocytes was increased in both severe COVID-19 and gout patient groups compared to healthy controls. Differential expression analysis and MR analysis showed that NLRP3 was positively associated with the risk of severe COVID-19 and involved 11 SNPs, of which rs4925547 was not significantly co-localized. In contrast, IER3 was positively associated with the risk of gout and involved 9 SNPs, of which rs1264372 was significantly co-localized. Discussion: Monocytes have a complex role in gout flare and severe COVID-19, which underscores the potential mechanisms and clinical significance of the interaction between the two diseases.