Hellwege, Jacklyn N. and Edwards, Digna R. Velez and Giri, Ayush and Qiu, Chengxiang and Park, Jihwan and Torstenson, Eric S. and Keaton, Jacob M. and Wilson, O. D. and Robinson-Cohen, Cassianne and Chung, Cecilia P. and Roumie, Christianne L. and Klarin, Derek and Damrauer, Scott M. and DuVall, Scott L. and Siew, Edward and Akwo, Elvis A. and Wuttke, Matthias and Gorski, Mathias and Li, Man and Li, Yong and Gaziano, J. Michael and Wilson, Peter W. F. and Tsao, Philip S. and O'Donnell, Christopher J. and Kovesdy, Csaba P. and Pattaro, Cristian and Koettgen, Anna and Susztak, Katalin and Edwards, Todd L. and Hung, Adriana M. (2019) Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program. NATURE COMMUNICATIONS, 10: 3842. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; MEAN PLATELET VOLUME; SICKLE-CELL TRAIT; PARTITIONING HERITABILITY; SUSCEPTIBILITY LOCI; GENETIC-VARIATION; FUNCTION DECLINE; APOL1 RISK; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 09:46 |
| Last Modified: | 31 Mar 2020 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26407 |
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