A Genome-Wide Scan for Type 2 Diabetes in African-American Families Reveals Evidence for a Locus on Chromosome 6q

Abstract

African Americans are at increased risk of type 2 diabetes and many diabetes complications. We have carried out a genome-wide scan for African American type 2 diabetes using 638 affected sibling pairs (ASPs) from 247 families ascertained through impaired renal function to identify type 2 diabetes loci in this high-risk population. Of the 638 ASPs, 210 were concordant for diabetes with impaired renal function. A total of 390 markers, at an average spacing of 9 cM, were genotyped by the Center for Inherited Disease Research (CIDR) as part of the International Type 2 Diabetes Linkage Analysis Consortium. Nonparametric linkage (NPL) analyses conducted using the exponential model implemented in Genehunter Plus provided suggestive evidence for linkage at 6q24-q27 (163.5 cM, logarithm of odds [LOD] 2.26). Multilocus NPL regression analysis identified the 6q locus (D6S1035, LOD 2.67) and two additional regions: 7p (LOD 1.06) and 18q (LOD 0.87) as important in this model. NPL regression-based interaction analyses and ordered subset analyses (OSAs) supported the presence of a locus at chromosome 7p (29–34 cM) in the pedigrees with the earliest mean age of diagnosis of type 2 diabetes (P = 0.009 for interaction, ΔP = 0.0034 for OSA) and lower mean BMI (P = 0.009 for interaction, ΔP = 0.070 for OSA). These results provide evidence that genes predisposing African-American individuals to type 2 diabetes are located in the 6q and 7p regions of the genome.