Genetic association between immune cells and gout: A Mendelian randomization study

Abstract

Abstract Background Numerous studies have demonstrated a significant correlation between immune cells and the initiation and progression of gout. Nevertheless, the existing body of evidence concerning immune cells implicated in gout and the establishment of a causal relationship remain limited. Objective To evaluate the causal connection between immune cells and gout, Mendelian randomization (MR) analysis was conducted using single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Methods This investigation revealed genetic variations known as single-nucleotide polymorphisms (SNPs) associated with 731 immune cell signatures from the International Working Group (IEU) open genome-wide association study (GWAS). The gout-associated GWAS dataset was obtained from ebi-a-GCST001790. The finn-b-M13_GOUT dataset was subsequently used for validation. We conducted MR analyses separately for the two gout datasets, followed by a meta-analysis. Causal effects were estimated using the inverse variance weighted (IVW) and MR‒Egger methods for MR analyses. Horizontal pleiotropy, heterogeneity and leave-one-out analyses were performed for sensitivity analysis. SNP annotations were performed to identify significant risk genes associated with immune cells and gout. Results IVW analyses revealed that 42 and 45 immunophenotypes were causally associated with gout in the discovery dataset and the validation dataset, respectively. A meta-analysis of the MR estimates from the two datasets revealed that CD25 on CD39 + CD4 + T cells and CD11b on CD14 + monocytes were risk factors for gout, while CD27 on switched memory B cells was a protective factor against gout. No evidence was found for horizontal pleiotropy or heterogeneity in the sensitivity analysis of any causal associations. At the locus-wide significance level of immunophenotyping, we annotated SNPs and identified 46 host genes that may be associated with the pathogenesis of gout. Conclusion The present study used MR analysis to demonstrate the causal associations between immune cells and gout via genetic means. This study provides some instructive suggestions for clinical treatment and experimental research in the future.