Genetics of Type 2 Diabetes in West Africans
- Type 2 diabetes (T2D) and associated complications are major contributors to the global disease burden. T2D is already a major health threat in populations in developed countries and is rapidly taking hold in the developing world.
- It is believed that understanding the complex interplay between genetic and lifestyle characteristics in the etiology of T2D and related complications will lead to the development of better preventive and therapeutic strategies. In Addition, the results of this project will facilitate our understanding of causes of diabetes in African Americans, other US and world populations
- To conduct a genome-wide association study (GWAS) to identify susceptibility genetic variants for diabetes among the Yoruba people in Ibadan, Nigeria.
- To enroll and examine 300 unrelated cases of T2D and 300 ethnicity-matched Yoruba controls.
- To conduct resequencing of positional candidate gene/loci to identify likely functional variants in a subset of the cohort.
- To conduct replication studies of the top-100 scoring variants in three independent African and European ancestry samples.
- To investigate whether diabetes-associated variants discovered in European populations increase diabetes risk in West Africans.
- Patients 25 years of age with confirmed T2D who are newly diagnosed or on treatment of Yoruba ethnicity in Ibadan, Nigeria. Control subjects are nondiabetics ethnically matched to patients.
- The study design for both patients and controls consists of the following steps:
- Discuss informed consent process and obtain signed informed consent form. Informed consent will be administered by trained clinic staff.
- Assign study ID (barcode)
- Administer questionnaires
- Obtain spot urine sample
- Measure blood pressure
- Obtain anthropometric measurements including body composition
- Perform finger prick for blood glucose level
- Obtain venous blood samples
- Perform eye examination
- On the following day, perform confirmatory blood glucose for the small subset of participants requiring confirmation of previous test result DNA extraction of stored samples will be done at either the National Institutes of Health or the laboratory in Nigeria.
- GWAS will be conducted using publicly available software packages.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Genetics of Type 2 Diabetes in Diverse Populations|
|Study Start Date:||January 2009|
This research protocol is designed to study the genetic basis of Type 2 Diabetes (T2D) in a broad range of populations in the United States and abroad. This project takes advantage of the well established infrastructure and success of Dr. Rotimi's international genetic epidemiology study of T2D funded as an R01 grant by NIDDK while he was at Howard University. This parent project is ongoing in four major ethnic groups in Nigeria (Yoruba and Ibo) and Ghana (Akan and Gaa). At completion in 2013 and given current projections, we anticipate enrolling about 2,000 cases and 2000 controls from the five centers in West Africa (Enugu, Ibadan and Lagos in Nigeria; Accra and Kumasi in Ghana). However, current projection indicates that the enrollment of Yoruba cases and controls will be short by about 300 cases and 300 controls. It is critically important to supplement the enrollment of Yoruba participants from another community in the Ibadan metropolitan area in Nigeria. Therefore, the original goal of the current project is to enroll additional 300 cases of T2D and 300 ethnically matched Yoruba controls to facilitate the conduct of genome-wide association study (GWAS) and candidate gene/loci studies in West Africans. Other current and future projects will increase the number of subjects for future genome-wide association studies (GWAS), linkage disequilibrium (LD) mapping, and functional studies in different ethnically-defined populations. Each project will aim to enroll ethnically balanced cases and controls with the goal of facilitating the conduct of GWAS and candidate gene/loci studies in a broad range of populations. Overall, these studies aim to further (or in some cases be the first) such large-scale efforts to understand the genetic basis of T2D in individuals of varying backgrounds including African and Mexican ancestries. Identified candidate genes/loci will be investigated by re-sequencing and functional studies will be conducted to identify susceptibility variants for diabetes and associated complications including obesity, hypertension, nephropathy, neuropathy and retinopathy. Additionally, these samples will be used to study genetic variation in the context of how participants of different ancestry respond to drugs and other environmental factors and how this variation may have shaped population history. Given past activities, it is also anticipated that this resource will form the basis of multiple collaborations between Dr. Rotimi's lab, several NIH intramural researchers and non-NIH scientists. Each subsequent population that is added to this study over time will use the same procedures that were originally approved for ongoing work among West Africans.
|Contact: Shirley Freeman||(301) firstname.lastname@example.org|
|Contact: Charles N Rotimi, M.D.||(301) email@example.com|
|University College Hospital||Recruiting|
|Principal Investigator:||Charles N Rotimi, M.D.||National Human Genome Research Institute (NHGRI)|