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• W2123149457 abstract "Genome-wide association studies (GWASs) have identified multiple loci associated with the risk of CKD. Almost all risk variants are localized to the noncoding region of the genome; therefore, the role of these variants in CKD development is largely unknown. We hypothesized that polymorphisms alter transcription factor binding, thereby influencing the expression of nearby genes. Here, we examined the regulation of transcripts in the vicinity of CKD-associated polymorphisms in control and diseased human kidney samples and used systems biology approaches to identify potentially causal genes for prioritization. We interrogated the expression and regulation of 226 transcripts in the vicinity of 44 single nucleotide polymorphisms using RNA sequencing and gene expression arrays from 95 microdissected control and diseased tubule samples and 51 glomerular samples. Gene expression analysis from 41 tubule samples served for external validation. 92 transcripts in the tubule compartment and 34 transcripts in glomeruli showed statistically significant correlation with eGFR. Many novel genes, including ACSM2A/2B, FAM47E, and PLXDC1, were identified. We observed that the expression of multiple genes in the vicinity of any single CKD risk allele correlated with renal function, potentially indicating that genetic variants influence multiple transcripts. Network analysis of GFR-correlating transcripts highlighted two major clusters; a positive correlation with epithelial and vascular functions and an inverse correlation with inflammatory gene cluster. In summary, our functional genomics analysis highlighted novel genes and critical pathways associated with kidney function for future analysis." @default.
• W2123149457 created "2016-06-24" @default.
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• W2123149457 date "2014-09-17" @default.
• W2123149457 modified "2023-10-13" @default.
• W2123149457 title "Functional Genomic Annotation of Genetic Risk Loci Highlights Inflammation and Epithelial Biology Networks in CKD" @default.
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• W2123149457 doi "https://doi.org/10.1681/asn.2014010028" @default.
• W2123149457 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4341476" @default.
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