A genome-wide scan for type 2 diabetes in African-American families reveals evidence for a locus on chromosome 6q.
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, DeltaP = 0.0034 for OSA) and lower mean BMI (P = 0.009 for interaction, DeltaP = 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.
Sale
Michèle M
MM
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. msale@wfubmc.edu
Freedman
Barry I
BI
Langefeld
Carl D
CD
Williams
Adrienne H
AH
Hicks
Pamela J
PJ
Colicigno
Carla J
CJ
Beck
Stephanie R
SR
Brown
W Mark
WM
Rich
Stephen S
SS
Bowden
Donald W
DW
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017668:Age of Onset; D000419:Albuminuria; D015992:Body Mass Index; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005819:Genetic Markers; D015894:Genome, Human; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008126:Lod Score; D010641:Phenotype; D018709:Statistics, Nonparametric; D014481:United States
D005819:Genetic Markers; D006442:Glycated Hemoglobin