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Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments.
Sheng, Xin; Guan, Yuting; Ma, Ziyuan; Wu, Junnan; Liu, Hongbo; Qiu, Chengxiang; Vitale, Steven; Miao, Zhen; Seasock, Matthew J; Palmer, Matthew; Shin, Myung K; Duffin, Kevin L; Pullen, Steven S; Edwards, Todd L; Hellwege, Jacklyn N; Hung, Adriana M; Li, Mingyao; Voight, Benjamin F; Coffman, Thomas M; Brown, Christopher D; Susztak, Katalin.
Afiliação
  • Sheng X; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Guan Y; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Ma Z; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Wu J; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Liu H; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Qiu C; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Vitale S; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Miao Z; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Seasock MJ; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Palmer M; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Shin MK; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Duffin KL; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Pullen SS; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Edwards TL; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Hellwege JN; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Hung AM; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Li M; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Voight BF; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Coffman TM; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
  • Brown CD; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Susztak K; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Nat Genet ; 53(9): 1322-1333, 2021 09.
Article em En | MEDLINE | ID: mdl-34385711
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Locos de Características Quantitativas / Insuficiência Renal Crônica / Hipertensão / Túbulos Renais Distais / Túbulos Renais Proximais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Locos de Características Quantitativas / Insuficiência Renal Crônica / Hipertensão / Túbulos Renais Distais / Túbulos Renais Proximais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA