Genetics of Obesity, Diabetes, and Heart Disease in African Diaspora Populations

Diabetes Clinical Trial

Official title: Genetics of Obesity, Diabetes, and Heart Disease in African Diaspora Populations

Status Enrolling by invitation

Clinical Trial Summary

Background:

• African Americans have one of the highest rates of type 2 diabetes in the United States, and often have other medical problems related to obesity and cardiovascular disease. These conditions have various risk factors, including high blood sugar levels, high cholesterol levels, and insulin resistance. However, these risk factors have not been studied very closely in individuals with African ancestry, including Afro-Caribbean and sub-Saharan Africa migrant populations. Researchers are interested in conducting a genetic study on obesity, adult-onset diabetes, heart disease, and other common health conditions in individuals with African ancestry.

Objectives:

• To collect genetic and non-genetic information from individuals with African ancestry to study common health conditions related to obesity, adult-onset diabetes, and heart disease.

Eligibility:

• Individuals at least 18 years of age who self-identify as African American, Afro-Caribbean, or migrants from sub Saharan Africa.

Design:

• Participants will undergo a physical examination and will provide a blood sample for study.

• Participants will also answer questions about personal and family medical history and current lifestyle behaviors.

• No treatment will be provided as part of this protocol....

Clinical Trial Description

Study Design:

The study is comprised of a population-based sample from Dr. Anne Sumner s ongoing NIDDK studies to perform a quantitative trait analysis of multiple metabolic biomarkers and disorders including T2D, hypertension, CVD and obesity in a total of 1000 people of African ancestry and approximately100 whites (who will serve as a comparison group) residing in the United States. Because some of the identified variants will be rare, we will use the methods proposed by Li and Leal. Under an additive model and at a MAF of 0.04, this sample size has 80% power to detect a genetic effect that may explain a 1-4 unit change depending on the trait in question (e.g., BMI in kg/m^2, blood glucose in mg/dL, systolic and diastolic BP in mmHG).

We will also perform exome sequencing of 48 cases of African descent and genotype identified variants in the larger cohort. Cases for exome sequencing will consist of individuals who have more than one metabolic condition, i.e., diabetes, pre-diabetes, obesity, hypertension and/or dyslipidemia. We propose to carry out exome capture of 48 individuals (96 chromosomes). Given the probability of observing a specific allele one or more times of 1 - (1-p)^2N (where p is the minor allele frequency), a sample of 48 individuals (96 chromosomes) provides a 99% probability of finding a sequence variant with a minor allele frequency (MAF) of 0.05, 98% probability of finding a variant with an MAF of 0.04, 95% probability of finding a variant with an MAF of 0.03, 86% probability of finding a variant with an MAF of 0.02 and 62% probability of finding a variant with an MAF of 0.01. We will use four main filters to identify potential variants with functional consequences. We will look for 1) SNPs that are intragenic or in promoter regions, 2) SNPs that cause nonsynonymous coding changes according to Polyphen and SIFT, 3) nonsense mutations, and 4) missense mutations that have possible or probable damaging protein effects. All selected SNPs will be tested for potential association with all metabolic parameters in this study.

Primary Objective:

Genotype variants of interest from genetic epidemiology studies conducted in Dr. Rotimi s lab in these individuals, with thorough clinical measurements available, in order to investigate biological mechanisms underlying observed associations.

Secondary Objectives:

Conduct whole-exome capture on a subset of cases with at least 2 metabolic disorders (i.e., diabetes, pre-diabetes, obesity, hypertension and/or dyslipidemia). Genotype identified variants in the larger cohort of 1000 persons or in existing studies of African ancestry individuals (Howard University Family Study or Africa America Diabetes Mellitus Study).

Exploratory Objectives:

Endpoints: Obesity, Metabolic Syndrome, Dyslipidemia, Pre-Diabetes, and Diabetes ;

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes
• Diabetes Mellitus
• Heart Diseases

• NCT number: NCT01316783
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Enrolling by invitation
• Start date: May 6, 2011