Type 2 diabetes has a devastating impact in the African American population. This grant proposal is the competitive renewal application for R01 DK663581 """"""""Genetics of African American Type 2 Diabetes."""""""" In the prior grant period extensive recruitment, genotyping, and analysis was carried out with the goal of identifying genetic loci which contribute to risk for type 2 diabetes (T2DM) in the African American population. Genetic risk factors for T2DM in African Americans appear largely different from those previously identified in European-derived populations. Thus, identification of T2DM loci in African Americans will not only provide insight into diabetes susceptibility in this high risk population, but will potentially identify novel pathways of diabetes risk. These studies have culminated in performance of the first Genome Wide Association Study (GWAS) of T2DM in African Americans.
Specific aims of the study are to 1. Carry out a comprehensive analysis of the GWAS data;2. Genotype high scoring SNPs from the GWAS in a two stage replication analysis consisting of a first stage of 1000 independent cases and 1000 controls, followed by further replication in a large collection of study samples containing T2DM and controls;3. Perform a Meta-analysis of Wake Forest data with GWAS data from the Candidate Gene Association Resource (CARe) Project and the Family Investigation of Nephropathy in Diabetes (FIND) study resulting in a total of over 17,000 African American samples to confirm T2DM associations and identify genes contributing smaller effect sizes;and 4. Subject replicated loci to a combination of bioinformatic, molecular, and analytical approaches to comprehensively characterize variants/loci/genes which are associated with T2DM in African Americans. Successful completion of these aims will set the stage for future studies of mechanism of action of these loci at molecular, cellular, and organism levels to contribute to the long term goal of this work: to improve the prediction, prevention, and treatment of T2DM in African Americans.

Public Health Relevance

This study is focused on identifying the gene which contributes to type 2 diabetes susceptibility 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 #
5R01DK066358-08
Application #
8457008
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Mckeon, Catherine T
Project Start
2003-09-30
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
8
Fiscal Year
2013
Total Cost
$440,543
Indirect Cost
$142,879
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
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Guan, Meijian; Keaton, Jacob M; Dimitrov, Latchezar et al. (2018) An Exome-wide Association Study for Type 2 Diabetes-Attributed End-Stage Kidney Disease in African Americans. Kidney Int Rep 3:867-878
Keaton, Jacob M; Gao, Chuan; Guan, Meijian et al. (2018) Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans. Genet Epidemiol 42:559-570
Manning, Alisa (see original citation for additional authors) (2017) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes 66:2019-2032
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Keaton, Jacob M; Hellwege, Jacklyn N; Ng, Maggie C Y et al. (2017) 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
Fuchsberger, Christian (see original citation for additional authors) (2016) The genetic architecture of type 2 diabetes. Nature 536:41-47
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
Ng, Maggie C Y (2015) Genetics of Type 2 Diabetes in African Americans. Curr Diab Rep 15:74
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

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