Genetics of African American Type 2 Diabetes Project Summary: Type 2 diabetes (T2D) is highly prevalent in the US with higher prevalence in the minority populations (9- 13.2%) as compared to non-Hispanic whites (7.6%). Efforts from large multi-ancestry consortia using genome- wide association studies (GWAS) approaches have successfully identified a large number of genetic variants associated with T2D. However, the majority of disease heritability remains unexplained and identification and characterization of the respective causal loci is limited. This is especially true for African Americans, the focus of this application, in which have led genetic exploration of type 2 diabetes genetics. Building on our establishment of the largest GWAS in African Americans in the Meta-analysis of Type 2 Diabetes in African Americans (MEDIA) Consortium and ongoing collaborations with other consortia on T2D and related traits, this project aims to use integrative phenomics analyses of genomics, metabolomics and transcriptomics in well- characterized samples to achieve the following specific aims.
Aim 1 : GWAS meta-analysis of baseline and dynamic glucose homeostasis traits and identification of functional variants and target genes using genomics and metabolomics.
Aim 2 : Integration of genomics, metabolomics and transcriptomics to identify functional variants and target genes for T2D.
Aim 3 : Integration of functional annotations, cross-trait associations and gene-gene/gene environment interactions to fine map T2D related loci and discover novel loci in African American and trans-ancestry GWAS.

Public Health Relevance

This study aims to integrate genomics, metabolomics and transcriptomics to identify and characterize genetic loci that contribute to type 2 diabetes and related traits in multiple populations, with focus on African Americans. The study will contribute to improved prediction, prevention, and treatment of type 2 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066358-13
Application #
9781693
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Zaghloul, Norann
Project Start
2003-09-30
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
13
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
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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
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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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