Abstract

Type 2 diabetes (T2D) is highly prevalent in the US with higher prevalence in the minority populations (9-15.9%) as compared to non-Hispanic whites (7.6%). Efforts from large multi- ancestry consortia using genome-wide association studies (GWAS) and next generation sequencing approaches have successfully identified a large number of common and low frequency genetic variants associated with T2D. However, the majority of disease heritability remains unexplained and identification and characterization of the respective causal variants is limited. This project aims to use multi-ancestry GWAS meta-analysis complemented with novel analytical approach, as well as phenomic studies in well-characterized samples to achieve the following specific aims.
Aim 1 : Discovery and fine mapping of T2D loci using GWAS imputed to ancestry-specific reference panels for trans-ancestry GWAS meta-analysis.
Aim 2 : Targeted gene-gene and gene-environment interaction to identify novel T2D loci for trans-ancestry GWAS meta-analysis.
Aim 3 : Integrative Phenomics analyses of comprehensively characterized datasets using clinical metabolic, genomics, transcriptomics, and metabolomics for functional characterization of variants and loci associated with T2D.

Public Health Relevance

This study aims to identify, fine map, and characterize genetic loci that contribute to type 2 diabetes in multiple populations, with focus on African Americans. The study will contribute to improved prediction, prevention, and treatment of type 2 diabetes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
7U01DK105556-05
Application #
9830378
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Zaghloul, Norann
Project Start
2018-12-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2021-04-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232

  Publications

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
Lin, Xiaochen; Chan, Katie Kei-Hang; Huang, Yen-Tsung et al. (2018) Genetic Determinants for Leisure-Time Physical Activity. Med Sci Sports Exerc 50:1620-1628
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