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Diabetes 53:830-837, 2004
© 2004 by the American Diabetes Association, Inc.

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

Michèle M. Sale1,2, Barry I. Freedman2, Carl D. Langefeld3, Adrienne H. Williams3, Pamela J. Hicks1,4, Carla J. Colicigno1,4, Stephanie R. Beck3, W. Mark Brown3, Stephen S. Rich3, and Donald W. Bowden1,2,4

1 Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
2 Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
3 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
4 Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina

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, {Delta}P = 0.0034 for OSA) and lower mean BMI (P = 0.009 for interaction, {Delta}P = 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.

Address correspondence and reprint requests to Michèle M. Sale, PhD, Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. E-mail: msale{at}wfubmc.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.