Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs
Han, S. K.; McNulty, M. T.; Benway, C. J.; Wen, P.; Greenberg, A.; Onuchic-Whitford, A. C.; NEPTUNE, ; Wilson, P. C.; Humphreys, B. D.; Wen, X.; Han, Z.; Lee, D.; Sampson, M. G.
Show abstract
Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5,371 GLOM and 9,787 TUBE eQTLs by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an "integrative prior" for Bayesian statistical fine mapping. The use of an integrative prior resulted in higher resolution eQTLs illustrated by (1) smaller numbers of variants in credible sets with greater confidence, (2) increased enrichment of partitioned heritability for GWAS of two kidney traits, (3) an increased number of variants colocalized with the GWAS loci, and (4) enrichment of computationally predicted functional regulatory variants. A subset of variants and genes were validated experimentally in vitro and using a Drosophila nephrocyte model. More broadly, this study demonstrates that tissue-specific eQTL maps informed by single-nucleus open chromatin data have enhanced utility for diverse downstream analyses.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Age-Dependent Changes in the Progenitor Translatome Coordinated in part by Tsc1 Increase Perception of Signaling Inputs to End Nephrogenesis 96%
- Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle 95%
- The chromatin landscape of healthy and injured cell types in the human kidney 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments 95%
- Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function 95%
- In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.