Sale Michèle M, Lu Lingyi, Spruill Ida J, Fernandes Jyotika K, Lok Kerry H, Divers Jasmin, Langefeld Carl D, Garvey W Timothy
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
Diabetes. 2009 Jan;58(1):260-7. doi: 10.2337/db08-0198. Epub 2008 Oct 3.
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).
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.
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).
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.
来自南卡罗来纳州海岛的讲古拉语的非裔美国人具有欧洲人基因混合程度低、2型糖尿病及糖尿病并发症发病率高的特点。通过海岛非裔美国人基因登记处(SUGAR项目)招募了患有2型糖尿病的患病亲属对。
我们进行了全基因组连锁扫描,对197个家系中的471名患病个体和50名未患病亲属的5974个单核苷酸多态性进行基因分型。使用多点引擎进行快速似然推断分析数据,并对2型糖尿病诊断年龄、腰围、腰臀比和体重指数进行有序子集分析(OSA)。我们使用条件逻辑回归似然法搜索异质性和相互作用。
在14号染色体123 - 124厘摩处检测到2型糖尿病的连锁峰(优势对数[LOD]为2.10),以及2型糖尿病诊断年龄较晚的亚组的连锁峰(最大LOD为4.05)。在7号染色体上,44 - 45厘摩处检测到2型糖尿病的一个连锁峰(LOD为1.18),78厘摩处检测到2型糖尿病的另一个连锁峰(LOD为1.64),以及2型糖尿病诊断年龄较早的亚组的连锁峰(最大LOD为3.93)。在多位点模型中,14号染色体位点和7号染色体上29.5厘摩处的一个峰被确定为重要位点。其他提供适度连锁证据的区域包括1号染色体167.5厘摩处(LOD为1.51)和3号染色体121.0厘摩处(LOD为1.61)。
本研究在非裔美国人的14q染色体上发现了一个新的2型糖尿病位点,该位点似乎可降低疾病发病年龄,并在7号染色体上确认了两个位点。