A functional genomics pipeline for genetic discovery in diabetic kidney disease
Active Project Grant Awarded Last action
- Award ID
- R01DK132299
- Recipient
-
The Broad Institute, Inc. UEI H5G9NWEFHXN4
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $5,171,202
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date 87% complete
- Place of performance
- Cambridge, MA 02142, USA
Award details come from USAspending.gov.
Description
- Abstract
- Diabetic kidney disease (DKD) is a devastating microvascular complication of both type 1 (T1D) and type 2 diabetes (T2D). IT has been shown to have a heritable component, but prior searches for the genetic determinants of this condition have had limited success. In the genetics of nephropathy - an international effort (genie) consortium, a collaboration between queen's university belfast, university of dublin, university of helsinki, university of michigan, university of pennsylvania and the broad institute, we have leveraged an ongoing CO-funding mechanism between ireland, northern ireland and the US. This international genomics consortium enucleated a larger diabetic nephropathy collaborative research initiative, which coalesced to assemble nearly 20,000 samples from participants with T1D, with and without kidney disease. We performed a genome-wide association study (gwas) and discovered 16 new signals at genome-wide significance. The strongest signal centered on a protective missense coding variant at COL4A3, which encodes an integral component of the glomerular basement membrane, implicating this aspect of kidney biology in DKD. In this award, we propose to build on this established infrastructure to undertake the following specific aims: (1) to significantly expand our sample size by including ~150,000 samples with DKD in the context of T2D, thereby substantially increasing our power to discover shared and distinct risk factors for DKD in T1D and T2D, and to use computational tools to derive biological insights into DKD pathogenesis; (2) to generate a genome-wide epigenomic dataset in both peripheral blood and human kidney to inform the relevance of genetic findings, enable the construction of predictive tools, and infer causality via mendelian randomization; and (3) to create an experimental pipeline centered on animal, cellular and organoid models of DKD to pursue functional validation of promising genetic findings. This ongoing close collaboration of multidisciplinary and synergistic research groups should advance our knowledge of the molecular determinants of DKD, identify potential molecular targets for therapeutics, and facilitate clinical prediction.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $615,979 | |
| Amendment | $622,668 | |
| Amendment | $600,931 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $631,482 | |
| Amendment | $631,482 | |
| Amendment | $631,482 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $718,589 | |
| Original award | $718,589 |
Show all 15
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of California, San Diego | $39,369 | |
| The Regents Of The University Of Colorado | $21,593 | |
| The Trustees Of The University Of Pennsylvania | $74,776 | |
| Regents Of The University Of Michigan | $122,346 | |
| University Of California, San Diego | $39,008 | |
| The Regents Of The University Of Colorado | $19,676 | |
| Regents Of The University Of Michigan | $122,269 | |
| Vanderbilt University Medical Center | $68,043 | |
| Subrecipient not on record | $104,314 | |
| National University Hospital (Singapore) PTE LTD | $23,858 | |
| The Trustees Of The University Of Pennsylvania | $71,152 | |
| University Of California, San Diego | $41,887 | |
| Vanderbilt University Medical Center | $75,688 | |
| Subrecipient not on record | $110,982 | |
| Regents Of The University Of Michigan | $130,962 | |
| The Regents Of The University Of Colorado | $20,488 | |
| National University Of Singapore | $25,920 | |
| The Trustees Of The University Of Pennsylvania | $77,318 |
Show all 18
Quick answers
Who received award R01DK132299?
R01DK132299 was awarded to The Broad Institute, Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on August 1, 2022.
How much is award R01DK132299 worth?
$5,171,202 has been obligated on R01DK132299.
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