Exploring Potential Novel Causal Genes for Chronic Kidney Disease
Exploring Potential Novel Causal Genes for Chronic Kidney Disease
Fangyi Hao1, Tian Tian1, Zhen Yang1 and Jiaxin Zheng2*
ABSTRACT
Functional genes underlying chronic kidney disease (CKD) remain unclear. This work explored susceptibility genes related to serum creatinine (Scr) and CKD through Mendelian randomization (MR) analysis.Data from genome-wide association study (GWAS) were selected, with Scr, single nucleotide polymorphisms (SNPs), and CKD as exposure factor, instrumental variables, and outcome variable, respectively. SNPs related to Scr and CKD were screened with P<5.0×10-8 and r2=0.001. Correlation between Scr and CKD was analyzed using inverse variance-weighted (IVW), MR-Egger regression, and weighted median estimator (WME). Intercept term of the MR-Egger method was adopted to assess the SNP sensitivity. Genes regulated by SNPs were identified in the eQTL database, and the intersecting target genes were subjected to GO analysis. Furthermore, interactions among proteins were predicted using the Search Tool for the Retrieval of Interacting Genes (STRING) database.47 SNPs related to Scr and CKD were identified in the retrieved GWAS database. Results from the MR-Egger, WME, IVW, and Weighted mode methods all indicated a negative correlation (NC) between Scr and CKD (P<0.05). 22 SNPs regulated 19 genes, which were associated with various biological processes (BPs). Key genes associated with CKD were DAB2, UBE2Q2, KCNQ1, SHROOM3, and PRKAG2.A NC between Scr and CKD was observed. DAB2, UBE2Q2, KCNQ1, SHROOM3, and PRKAG2 were linked with CKD, providing new insights for understanding the pathogenesis of CKD and the design of drug targets.
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