Genetics of Type 2 Diabetes in West Africans

Genetics of Type 2 Diabetes in Diverse Populations

Background:

• 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

Objectives:

• 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.

Eligibility:

• Patients 18 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.

Design:

• 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 Description:

This protocol is designed to study the genetic basis of Type 2 Diabetes (T2D) and related conditions in Africa.

Objectives:

Primary Objective: To conduct genetic association studies of T2D, T2D complications, and related traits in Africans of diverse ethnic groups

Secondary Objectives:

• To investigate the contribution of gene x environment interactions in T2D risk and in influencing related traits
• To develop a large-scale genetic epidemiological resource for the replication of findings in other studies of related traits
• To conduct trans-ethnic fine-mapping
• To describe the study population epidemiologically in terms of cardiometabolic traits and prevalence of related conditions
• To conduct population genetic analyses to describe population history and to develop statistical techniques appropriate for genetic analyses of African ancestry individuals
• To conduct deep phenotyping to facilitate additional research questions related to cardiometabolic traits and for follow-up previous findings

Endpoints:

Primary Endpoint: T2D

Secondary Endpoints: T2D Complications, Hypertension, Obesity, Dyslipidemia, Metabolic Syndrome, Chronic Kidney Disease, and other cardiometabolic traits

• INCLUSION CRITERIA:

As our primary interest is in T2D, it is important to exclude individuals who may have diabetes of another etiology. Elevated blood glucose in individuals 25 years old or younger is unlikely (in West Africa) to result from T2D and may reflect Type 1 Diabetes. Therefore, only individuals older than 25 years will be included in this study.

We are seeking to enroll persons without T2D or with previously or newly diagnosed T2D. Previously diagnosed cases will be determined by self-report of being treated with oral medication or insulin. Newly diagnosed cases will be determined by fasting blood glucose value >= 126 mg/dl on more than one occasion. Individuals who have elevated blood glucose during their initial reading will be asked to return to the study site for a second test. If this test also has a fasting blood glucose value >= 126 mg/dl, then they will be considered a new case. The control group will be individuals with no report of T2D diagnosis and fasting plasma glucose (FPG)< 126 mg/dl.

Only unrelated individuals will be included in this phase of the study to avoid confounding genetic association studies by relatedness in the study population.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Incarceration.
• Lack capacity to consent to research participation.
• Pregnancy.