| Literature DB >> 34385711 |
Xin Sheng1,2,3, Yuting Guan1,2,3, Ziyuan Ma1,2,3, Junnan Wu1,2,3, Hongbo Liu1,2,3, Chengxiang Qiu1,2,3, Steven Vitale1,2,3, Zhen Miao1,2,3, Matthew J Seasock1,2,3, Matthew Palmer4, Myung K Shin5, Kevin L Duffin6, Steven S Pullen7, Todd L Edwards8, Jacklyn N Hellwege8, Adriana M Hung9, Mingyao Li10, Benjamin F Voight2,3,11,12, Thomas M Coffman13, Christopher D Brown3, Katalin Susztak14,15,16.
Abstract
The functional interpretation of genome-wide association studies (GWAS) is challenging due to the cell-type-dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTLs) for 659 microdissected human kidney samples and identified cell-type-eQTLs by mapping interactions between cell type abundances and genotypes. By partitioning heritability using stratified linkage disequilibrium score regression to integrate GWAS with single-cell RNA sequencing and single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing data, we prioritized proximal tubules for kidney function and endothelial cells and distal tubule segments for blood pressure pathogenesis. Bayesian colocalization analysis nominated more than 200 genes for kidney function and hypertension. Our study clarifies the mechanism of commonly used antihypertensive and renal-protective drugs and identifies drug repurposing opportunities for kidney disease.Entities:
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Year: 2021 PMID： 34385711 PMCID： PMC9338440 DOI： 10.1038/s41588-021-00909-9
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307