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; Hellwege, Jacklyn N; Ng, Maggie C Y et al. (2016) GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS. Pac Symp Biocomput 22:242-253
Ma, Lijun; Langefeld, Carl D; Comeau, Mary E et al. (2016) APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease. Kidney Int 90:389-95
Ma, Jun; Guan, Meijian; Bowden, Donald W et al. (2016) Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans. Clin J Am Soc Nephrol 11:1034-43
Guan, Meijian; Ma, Jun; Keaton, Jacob M et al. (2016) Association of kidney structure-related gene variants with type 2 diabetes-attributed end-stage kidney disease in African Americans. Hum Genet 135:1251-1262
Williams, Robert C; Elston, Robert C; Kumar, Pankaj et al. (2016) Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND). BMC Genomics 17:325
Bonomo, Jason A; Palmer, Nicholette D; He, John Cijiang et al. (2015) Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease. Am J Nephrol 42:259-64
Yeo, Nan Cher; O'Meara, Caitlin C; Bonomo, Jason A et al. (2015) Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity. Genome Res 25:57-65
Ng, Maggie C Y (2015) Genetics of Type 2 Diabetes in African Americans. Curr Diab Rep 15:74
Palmer, Nicholette D; Ng, Maggie C Y; Langefeld, Carl D et al. (2015) Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD. J Am Soc Nephrol 26:1021-5
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

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