查看文章

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 …