Integration Analysis Of Summary Data From GWAS And EQTL Studies Identified Potential Causal Chronic Kidney Disease Genes

Chronic kidney disease(CKD)is a syndrome which defined as a continuous change in kidney structure,function,or both.Serum creatinine(Scr)is an important indicator of clinical renal function.In recent years,the prevalence of chronic kidney disease worldwide has reached 7%-12%.Currently,Genome-wide association studies(GWAS)has identified many important genetic variants associated with chronic kidney disease.But from the genetic variants identified by GWAS,the genes which play a role in chronic kidney disease actually are still unknown.This study used summary data-based Mendelian randomization(SMR)to identify genes that have a causal relationship with chronic kidney disease and serum creatinine.This method used the SNP which has the most significant correlation with gene expression as a instrumental variable to study the causal relationship between gene expression and chronic kidney disease and serum creatinine;and used the protein-protein interaction network to explore the functional interaction between the proteins produced by the identified genes;at the same time,IPA(Ingenuity Pathway Analysis)was used to analyze the functional relationship between genes and diseases;Differential expression analysis was used to identify genes with differential expression in the chronic kidney disease group and healthy controls.The results showed that:1.The expression of six genes identified by the SMR method may cause changes in serum creatinine,namely DAB2,MANBA,RGS14,GGTL3,SDCCAG8 and SENP2,the SDCCAG8 and SENP2 genes among them were new genes related to serum creatinine.The GATM gene identified by SMR method was associated with chronic kidney disease significantly;2.The proteinprotein interaction network found that the GATM,SENP2 and SDCCAG8 have the interaction with the proteins which associated with chronic kidney disease;3.IPA analysis showed that GGTL3,DAB2,SENP2,SDCCAG8 and GATM genes were involved in different pathways directly or indirectly related to chronic kidney disease;4.Differential expression analysis showed that genes GATM and SENP2 were differently expressed in the CKD group and healthy controls.In summary,SENP2 is likely to be a potential new causal gene of CKD.This study identified the genes which may causes the chronic kidney disease,thus narrowing the range of candidate genes further.This provided new ideas for the understanding of pathogenesis of chronic kidney disease and the designing of drug targets.