The Sea Islands Genetic Network (SIGNET)

Recent genome-wide association studies (GWAS) have successfully identified genetic variants that influence diabetes risk in European populations, however most do not have a major impact on diabetes risk in populations of African descent. The African American (AA) population from the Sea Islands of coastal South Carolina and Georgia has high rates of type 2 diabetes, low levels of admixture, and in general, consume a diet rich in saturated fats. We postulate that this unique combination of ancestral and environmental factors results in a more consistent penetrance of diabetes risk alleles, as well as enrichment of risk alleles of African origin. The existing DNA samples and rich phenotypic data from the Sea Island Families Project comprise a unique resource for genetic studies of type 2 diabetes and related metabolic traits such as dyslipidemia. Our central hypothesis is that the increased risk for T2DM in AA compared with European American (EA) is due, in part, to susceptibility alleles of African origin, and that these alleles can be identified using a GWAS. The Specific Aims are to: 1) Identify genetic risk factors for type 2 diabetes utilizing DNA samples and data from the Sea Island Families Project, Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited from SC, GA, NC, and AL; and a GWAS approach; 2) Identify genetic contributors to lipoprotein subclasses in African Americans using the lipoprotein subclass profile (particle size and concentration for multiple subclasses of VLDL, LDL, and HDL) assessed by NMR at LipoScience, Inc., and the GWAS data from Aim 1. The rationale for this project is that identification and validation of novel pathophysiological pathways and informed selection of candidate genes for diabetes risk will inform development of new, targeted prevention and treatment strategies in this underserved, high risk population.]]>
Project SuGAR Project SuGAR enlisted medical clinics, churches, and established organizations on the Sea Islands to aid in identifying patients with T2DM who belong to families with multiple affected members. Inclusion criteria included at least one affected sibling pair, no more than one of the parents affected with T2DM, and at least one parent still living. All members of families meeting these minimal criteria were studied after obtaining informed consent. Project SuGAR assessed medical, anthropometrical, and metabolic information on affected and non-affected family members. The data are based on a multipage questionnaire, detailed family history and medical history, standardized blood pressures, physical examination, body dimensions and estimation of percent body fat, and laboratory testing. Blood pressure measurements were taken in the dominant arm with the patient having been in the sitting position for 5 minutes. Measurements were made using a calibrated, automated cuff device (DynaMap, New Brunswick, NJ); diastolic and systolic values represent the mean of the last two out of three sequential readings taken 3 minutes apart. Weights were determined using electronic calibrated scales (Detecto, Cleveland, OH) at 8-10AM after voiding and before breakfast. Heights were measured with a portable Harpenden statiometer. Standard arm, waist, hip and thigh circumferences were recorded using a tension-controlled tape measure (Novel Products, Rockton, IL). Body composition was assessed by standard caliper measurements of skin fold thickness in men and women, and also by segmental bioelectric impedance analyzer. Blood samples were drawn from all individuals. 20-40 ml was used for DNA extraction and 20 ml for laboratory tests. Laboratory testing included NMR lipid profiles; complete blood count; electrolytes; creatinine/BUN; liver function tests; hemoglobin A1C; fasting lipid panel (cholesterol, triglycerides, HDL); circulating islet cell antibodies (if diabetic); fasting glucose, insulin, C-peptide, proinsulin, and free fatty acids (FFA); and urine ACR. All non-diabetic family members have been evaluated with an oral glucose tolerance test (OGTT) with measurement of glucose and insulin. In the initial phases, all diabetic patients were also studied with an OGTT, however, approximately half-way through the study, OGTTs were discontinued as a time/cost saving measure in those patients in whom diabetes was clearly evident based on clinical grounds and fasting glucose level. The criteria established by the National Diabetes Data Group as modified by the Expert Committee of the American Diabetes Association were used to define diabetes status. COBRE Oral Health Additional AA diabetes patients have been recruited from the Sea Island population, as part of a previous South Carolina COBRE (Center of Biomedical Research Excellence) Oral Health pilot project, "An Epidemiological Study of Periodontal Disease and Diabetes: Cytokine Genes and Inflammation Factors" by Jyotika Fernandes, M.D. (MUSC). This is another study under the Sea Island Families Project umbrella. AA 18 years and older, with T2DM, living along the South Carolina border and 30 miles inland were included in the study. Type 1 diabetic individuals and edentulous patients were excluded from the study. All subjects answered a detailed questionnaire that focused on their medical and dental history. Blood and urine samples were collected for assessing diabetes control status and associated complications. These subjects underwent a single oral examination to document periodontal health. SLE in Gullah Health (SLEIGH) The Systemic Lupus Erythmatosus (SLE) in Gullah Health (SLEIGH) study (PI Gary Gilkeson, M.D.) is a population based case-control study of genetic and environmental risk factors for SLE. SLEIGH has been enrolling subjects since August 2003. All subjects have been enrolled through MUSC and the Medical College of Georgia. The inclusion criteria are: 1) age ≥2 years, 2) self-identification as AA Gullah from the Sea Islands region of South Carolina, with no known ancestors who were not of Gullah lineage, 3) having met at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE, 4) being able to speak and understand English, and 5) having the ability and willingness to give informed consent. First-degree relatives of the lupus probands are also invited to enroll. The subjects' parents and grandparents were also required to be of Sea Islands heritage. SLEIGH recruits healthy AA subjects from the Sea Islands community as age- and sex-matched controls, with the requirement that they must not have any history of autoimmune disease or known family members with SLE. In addition, these subjects had to have <4 positive responses on a connective tissue diseases screening questionnaire, and <3 of the ACR classification criteria for SLE. Blood and urine specimens are collected for DNA and disease activity labs. Reasons for Geographic and Racial Differences in Stroke (REGARDS) The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 AA and EA adults. Participants were randomly sampled with recruitment by mail then telephone. Individuals aged 45 years old and older were eligible for inclusion in the REGARDS cohort, for which enrollment began in February 2003. Exclusion criteria for REGARDS participation included active treatment for cancer; any serious medical condition which would prevent long-term participation; cognitive impairment as judged by the interviewer; living in a nursing home or on the waiting list for a nursing home; and a language barrier (speaks other than English). ]]>