Genome-Wide Linkage Scan in Gullah-Speaking African American Families With Type 2 Diabetes The Sea Islands Genetic African American Registry (Project SuGAR)

被引:22
|
作者
Sale, Michele M. [1 ,2 ,3 ]
Lu, Lingyi [4 ]
Spruill, Ida J. [5 ]
Fernandes, Jyotika K. [5 ]
Lok, Kerry H. [6 ]
Divers, Jasmin [4 ]
Langefeld, Carl D. [4 ]
Garvey, W. Timothy [6 ,7 ]
机构
[1] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA
[2] Univ Virginia, Dept Med, Charlottesville, VA USA
[3] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA
[4] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA
[5] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA
[6] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA
[7] Birmingham VA Med Ctr, Birmingham, AL USA
关键词
SINGLE NUCLEOTIDE POLYMORPHISMS; FACTOR-7-LIKE-2; TCF7L2; GENE; SUSCEPTIBILITY GENES; ASSOCIATION ANALYSIS; IDENTIFICATION; AFFINITIES; VARIANTS; MELLITUS; LOCUS; RISK;
D O I
10.2337/db08-0198
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR). RESEARCH DESIGN AND METHODS-We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, 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 type 2 diabetes (logarithm of odds [LOD] 2. 10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44-45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum 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) and chromosome 3 at 121.0 cM (LOD 1.61). CONCLUSIONS-This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7. Diabetes 58:260-267, 2009
引用
收藏
页码:260 / 267
页数:8
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