Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans
Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans
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DOI：
10.1086/302316
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发表时间：
1999-04-01
影响因子：
9.8
通讯作者：
Stern, MP
中科院分区：
文献类型：
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作者：
Duggirala, R;Blangero, J;Stern, MP
由于对2型糖尿病易感基因的染色体定位知之甚少，我们在墨西哥裔美国人中进行了全基因组扫描。我们使用的数据来自27个低收入的扩展墨西哥裔美国人家系，包括440个人的基因型数据可用于379个标记。我们使用方差成分技术对2型糖尿病（离散性状）和糖尿病发病年龄（截断的数量性状）两种表型进行多点连锁分析。对于多点分析，基于最佳间距和信息量选择了295个标记的子集。我们发现了重要的证据，即染色体10q上标记D10S587附近的易感基因座影响糖尿病发病年龄（LOD评分3.75），并且还与2型糖尿病本身相关（LOD评分2.88）。该易感基因座解释了糖尿病发病年龄总表型变异的63.8% ± 9.9%（P = .000016）和2型糖尿病易感性总变异的65.7% ± 10.9%（P = .000135）。较弱的证据发现糖尿病和发病年龄与染色体3p，4q和9p区域的联系。总之，我们最有力的证据表明，墨西哥裔美国人的糖尿病发病年龄和2型糖尿病本身与染色体10q上的一个区域有关。
Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8% +/- 9.9% (P = .000016) of the total phenotypic variation in age at onset of diabetes and 65.7% +/- 10.9% (P = .000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q.