Mendelian randomization study of the causal association between peripheral blood cell levels and IgA nephropathy

Objective To explore the causal relationship between peripheral blood cell levels (total white blood cells, neutrophils, monocytes, basophils, eosinophils, lymphocytes) and IgA nephropathy, and to provide genetic evidence for the association between peripheral blood cell levels and the risk of IgA nephropathy. Methods Single nucleotide polymorphisms related to total white blood cells, neutrophils, monocytes, basophils, eosinophils, and lymphocytes and summary level genetic data related to IgAN were obtained from published genome-wide association studies. The inverse variance weighting method was used for two-sample Mendelian randomization analysis. At the same time, MR-PRESSO and MR-Egger were used to detect pleiotropic effects, and sensitivity analysis was performed by 'leave-one-out ' method.Results In the study of the effect of peripheral blood cell level on IgAN, the IVW method showed that total white blood cells, neutrophils and eosinophils as risk factors were causally associated with the risk of IgAN. The P values of the intercept term of MR-Egger regression were all>0.05, that is, the selected SNP did not have gene pleiotropy, so Mendelian randomization was an effective method for causal inference in this study. There are four P<0.001 in the heterogeneity test results, so we should focus on the random effect IVW model. Conclusions After using the two-sample Mendelian randomization method to exclude confounding factors and reverse causal associations, the results of unbiased estimation can be obtained. Based on this, it can be determined that there is a causal relationship between total white blood cells, neutrophils, eosinophils and IgAN.