|
| Status |
Public on May 10, 2021 |
| Title |
Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The functional interpretation of GWAS remains challenging due to the cell-type dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTL) for 659 microdissected human kidney samples and identified cell-type eQTLs by mapping interactions between cell type abundance and genotype. By partitioning heritability using stratified LD-score regression to integrate GWAS with scRNA-seq and snATAC-seq data, we prioritized proximal tubules in kidney function and endothelial cells and distal tubule segments in 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.
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| |
|
| Overall design |
10x snATAC-seq for 2 human kidney samples
|
| |
|
| Contributor(s) |
Sheng X, Ma Z, Wu J, Susztak K |
| Citation(s) |
34385711, 34426578, 38287030, 38287344 |
| |
| Submission date |
Apr 13, 2021 |
| Last update date |
Feb 14, 2024 |
| Contact name |
Xin Sheng |
| E-mail(s) |
xin.sheng@pennmedicine.upenn.edu
|
| Organization name |
University of Pennsylvania
|
| Lab |
Susztak lab
|
| Street address |
3400 CCB
|
| City |
Philadelphia |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (2) |
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| Relations |
| BioProject |
PRJNA721690 |
| SRA |
SRP314697 |
