Genetic causality between 731 immune cell phenotypes and chronic kidney disease in Europeans: a bidirectional Mendelian randomization study

Abstract

Background Previous studies have demonstrated that various immune cell types are strongly associated with chronic kidney disease (CKD). However, the exact causal relationship is unclear. Methods Genome-wide association study (GWAS) summary statistics of 731 immune cell phenotypes and CKD were obtained from IEU OpenGWAS and FinnGen datasets, respectively. A bidirectional MR study was then performed to investigate the genetic causality between them using MR egger, weighted median, inverse variance weighted (IVW), simple mode and weighted mode, of which the results of IVW were considered to be the main ones. Finally, to identify whether the results of MR were reliable, sensitivity analyses were performed to detect heterogeneity and multiplicity, and a leave-one-out method was employed to check the stability. In addition, the FDR adjustment method was conducted to check the strength of genetic causality. Results Before FDR adjustment, 40 immune cell phenotypes were identified as genetically causative for CKD, and CKD was genetically causative for 33 immune cell phenotypes (P < 0.05). After FDR adjustment (P_FDR < 0.05), two immune cell phenotypes were identified as potentially genetically causative for CKD. However, there was no statistically significant genetic causality of CKD on immune cell phenotype (P_FDR > 0.05). At a looser threshold (P_FDR < 0.6), CKD was identified as potentially genetically causative for five immune cell phenotypes. Conclusion This study explores the genetic causality between immune cells and CKD through a genetic approach, which enhances the understanding of the interactions between immune responses and CKD, thereby offering directions for future clinical research.