Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-11704-w
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Funding
- VA grant [I01BX003360]
- VA Informatics and Computing Infrastructure (VINCI) [VA HSR RES 13-457]
- grants Genetics of Cardiometabolic Diseases in the VA Population [BX-003362-01]
- Veterans Affairs Office of Research and Development
- U.S. Department of Veterans Affairs [IK2-CX001870, I01-BX002641]
- VA Clinical Science research and Development investigator-initiated grant [CX000570-06]
- NIH/NHLBI [HL121429]
- Vanderbilt Molecular and Genetic Epidemiology of Cancer (MAGEC) training program [T32CA160056]
- Vanderbilt Genomic Medicine Training Program
- National Human Genome Research Institute of the National Institute of Health [T32HG008341]
- German Research Foundation [CRC 1140, CRC 992, KO 3598/3-1]
- DFG [CRC 1140, BO3815/4-1, KO 3598/4-1]
- Else Kroener Fresenius Forschungskolleg NAKSYS
- NIAMS [K23AR064768]
- Rheumatology Research Foundation
- NIH/NIDDK [K01DK109019]
- CTSA from NCATS/NIH [UL1TR000445]
- NIH [P50GM115305, U19HL065962]
- Vanderbilt-Ingram Cancer Center [P30 CA068485]
- Vanderbilt Vision Center [P30 EY08126]
- [1I01CX000982]
- [K12HD043483]
- [R01DK076077]
- [R01DK105821]
- [DP3DK108220]
- [1S10RR025141-01]
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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.
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