This proposal is a renewal resubmission application for R01 DK53591-09 "Mapping Genes for NIDDM Nephropathy in African Americans". The results of the first Genome Wide Association Study (GWAS) of African American diabetic nephropathy (performed in our laboratory), the ongoing NIDDK clinical research study, the Family Investigation of Nephropathy and Diabetes (FIND), and other resources will be combined to identify novel diabetic nephropathy genes in African Americans. This will be achieved by carrying out comprehensive genetic analysis of existing datasets, which will be extended by continued recruitment of African American diabetic nephropathy cases. The combined GWAS analysis (2,274 cases, 8,000 controls) will be followed by replication genotyping in up to 3,000 independent cases analyzed with data from 8,000 controls. Ultimately a combined analysis of greater than 5,000 cases and 16,000 controls will be possible. These efforts will lead to a comprehensive laboratory and computational analysis to investigate the genetic architecture of diabetic nephropathy genes. Results of the genetic analysis will be complemented with bioinformatic approaches to identify compelling candidate genes for susceptibility. These loci will be subjected to detailed molecular genetic analysis including resequencing (as appropriate), expression profiling, and motif identification to examine the functional basis of polymorphisms to define a molecular genetic mechanism for their contribution to diabetic nephropathy. Completion of these aims will contribute significantly to improving prediction, prevention, and treatment of this devastating disease that disproportionately affects the African American population.

Public Health Relevance

The goal of this project is to identify genes which contribute to diabetes associated kidney disease in the African American population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK053591-10A1
Application #
8293887
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Rasooly, Rebekah S
Project Start
1998-09-30
Project End
2016-02-29
Budget Start
2012-05-01
Budget End
2013-02-28
Support Year
10
Fiscal Year
2012
Total Cost
$638,223
Indirect Cost
$206,991
Name
Wake Forest University Health Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Keaton, Jacob M; Cooke Bailey, Jessica N; Palmer, Nicholette D et al. (2014) A comparison of type 2 diabetes risk allele load between African Americans and European Americans. Hum Genet 133:1487-95
Palmer, Nicholette D; Ng, Maggie C Y; Hicks, Pamela J et al. (2014) Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease. PLoS One 9:e88273
Bonomo, Jason A; Ng, Maggie C Y; Palmer, Nicholette D et al. (2014) Coding variants in nephrin (NPHS1) and susceptibility to nephropathy in African Americans. Clin J Am Soc Nephrol 9:1434-40
Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H et al. (2014) Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet 10:e1004517
Bonomo, Jason A; Palmer, Nicholette D; Hicks, Pamela J et al. (2014) Complement factor H gene associations with end-stage kidney disease in African Americans. Nephrol Dial Transplant 29:1409-14
Cooke Bailey, Jessica N; Palmer, Nicholette D; Ng, Maggie C Y et al. (2014) Analysis of coding variants identified from exome sequencing resources for association with diabetic and non-diabetic nephropathy in African Americans. Hum Genet 133:769-79
Monda, Keri L; Chen, Gary K; Taylor, Kira C et al. (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45:690-6
Lipkowitz, Michael S; Freedman, Barry I; Langefeld, Carl D et al. (2013) Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int 83:114-20
Ma, Lijun; Murea, Mariana; Snipes, James A et al. (2013) An ACACB variant implicated in diabetic nephropathy associates with body mass index and gene expression in obese subjects. PLoS One 8:e56193
Ng, Maggie C Y; Saxena, Richa; Li, Jiang et al. (2013) Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. Diabetes 62:965-76

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