A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array
A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array
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DOI：
10.2337/db07-0462
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发表时间：
2007-12-01
期刊：
影响因子：
7.7
通讯作者：
Knowler, William C.
中科院分区：
文献类型：
--
作者：
Hanson, Robert L.;Bogardus, Clifton;Knowler, William C.
目的是确定与糖尿病易感性的连锁不平衡中的遗传变异，在美国 - 印度人口中进行了一项针对年轻发病糖尿病的全基因组关联研究。研究设计和方法来自300例患有2型糖尿病的病例。随着发病年龄的年龄<25岁和334名非糖尿病对照受试者的年龄> = 45岁。为了提供家庭内关联的测试，包括121个病例受试者的非糖尿病兄弟姐妹以及140个对照组的糖尿病兄弟姐妹（172个sibships）。在Affymetrix 100K阵列上进行了基因分型，导致80,044个可用的单核苷酸多态性（SNP）。分析了SNP的家庭内部关联和案例和对照对象中的一般关联，这些测试通过Fisher的方法组合，优先于家庭内测试。回流 - p值较低的SNP比理论上的SNP较低。在无关联的全球无效假设下，有128个SNP的依据为p <0.001。这些SNP与糖尿病的关联进一步研究了来自人群研究的1,207名糖尿病患者和1,627名非糖尿病患者，这些人未纳入全基因组研究中。来自10个基因组区域的SNP显示了在p <0.05时复制的证据。其中包括在Znf659附近的3号染色体上的SNP，染色体I I附近的染色体I，ZBTB15附近的11号染色体11和SENP1附近的染色体12。Conclusions-conclusions-这些研究表明，这些区域表明，标记等位基因在与年轻人类型的变体中有潜在的标志性等位基因潜在的区域相位。美国印第安人的2种糖尿病。
OBJECTIVE-To identify genetic variants in linkage disequilibrium with those conferring diabetes susceptibility, a genome-wide association study for young-onset diabetes was conducted in an American-Indian population.RESEARCH DESIGN AND METHODS-Data come from 300 case subjects with type 2 diabetes with age of onset < 25 years and 334 nondiabetic control subjects aged >= 45 years. To provide for tests of within-family association, 121 nondiabetic siblings of case subjects were included along with 140 diabetic siblings of control subjects (172 sibships). Individuals were genotyped on the Affymetrix 100K array, resulting in 80,044 usable single nucleotide polymorphisms (SNPs). SNPs were analyzed for within-family association and for general association in case and control subjects, and these tests were combined by Fisher's method, with priority given to the within-family test.RESULTS-There were more SNPs with low P values than expected theoretically under the global null hypothesis of no association, and 128 SNPs had evidence for association at P < 0.001. The association of these SNPs with diabetes was further investigated in 1,207 diabetic and 1,627 nondiabetic individuals from the population study who were not included in the genome-wide study. SNPs from 10 genomic regions showed evidence for replication at P < 0.05. These included SNPs on chromosome 3 near ZNF659, chromosome I I near FANCF, chromosome 11 near ZBTB15, and chromosome 12 near SENP1.CONCLUSIONS-These studies suggest several regions where marker alleles are potentially in linkage disequilibrium with variants that confer susceptibility to young-onset type 2 diabetes in American Indians.