Single-cell RNA sequencing and Mendelian randomization to analyze regulatory role of key genes in IgA nephropathy
Objective To explore gene expression of key cell types in IgA nephropathy(IgAN)and regulatory role of key genes ADI1,BNIP3L and SERPINE2 in occurrence and development of IgAN.Methods The gene expression omnibus(GEO)and eQTLGen consortium database were used to perform Mendelian randomization(MR)and single-cell RNA sequencing(scRNA-seq).Key cell types of IgAN and causal relationship between ADI1,BNIP3L,SERPINE2 and IgAN were investigated.Expression profiles and screened out low expression genes were read through Seurat package,and used differential gene expression analysis to screen TOP100 highly expressed genes.In addition,were used sensitivity analysis and heterogeneity test were used to select significant results.Results ADI1(OR=0.946,95％CI:0.900-0.994,P=0.029),BNIP3L(OR=0.820,95％CI:0.707-0.950,P=0.008),SERPINE2(OR=0.958,95％CI:0.919-0.999,P=0.045)might be associated with a lower risk of IgAN.However,KLF6(OR=1.318,95％CI:1.036-1.678,P=0.025)was associated with high risk of IgAN.Conclusion Genetic characteristics of 18 key cell types including proximal renal tubule cells were revealed.ADI1,BNIP3L and SERPINE2 are closely related to the regulation of IgAN.
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