A genome-wide linkage scan in Gullah-speaking African American families with type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

Objective: The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes (T2DM) and diabetic complications. Affected relative pairs with T2DM were recruited through Project SuGAR (the Sea Islands Genetic African American Registry). Research Design and Methods: We conducted a genome-wide linkage scan, genotyping 5,974 SNPs in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using MERLIN, and ordered subsets analyses (OSA) for age at T2DM diagnosis, waist circumference, waist-to-hip ratio (WHR), and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach. Results: Linkage peaks on chromosome 14 at 123-124 cM were detected for T2DM (LOD 2.10) and the subset with later age at T2DM diagnosis (max. LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44-45 cM for T2DM (LOD 1.18), and 78 cM for T2DM (LOD 1.64) and the subset with earlier age at T2DM diagnosis (max. LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM, were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51), chromosome 3 at 121.0 cM (LOD 1.61). Conclusions: This study revealed a novel T2DM locus in an AA population on 14q that appears to reduce age of disease onset, and confirmed two loci on chromosome 7.