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

对患有 2 型糖尿病的格拉语非裔美国家庭进行全基因组连锁扫描:海岛非裔美国人遗传登记处(SuGAR 项目)

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Abstract

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.

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