A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study
A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study
复制标题
DOI：
10.2337/db07-1305
复制
发表时间：
2008-04-01
期刊：
影响因子：
7.7
通讯作者：
Polychronakos, Constantin
中科院分区：
文献类型：
--
作者：
Hakonarson, Hakon;Qu, Hui-Qi;Polychronakos, Constantin
我们全基因组关联（GWA）研究1型糖尿病的目标1阶段，检测到16p13处的一个基因座（p = 1.03 x 10（-10）），并在另外两个同类群中证实。在这里，我们描述了测试的结果，在这些额外的队列中，研究了统计显着性等级的下一个基因座。研究设计和方法 - 研究两个独立人群。 1型糖尿病遗传学联盟复制队列由549个家庭组成，至少一个患有糖尿病的儿童（946个受影响的儿童）和父母双方的DNA。加拿大复制队列由364个核家族组成，其中一个受1型糖尿病影响后代和两个父母（1,092个个体）。12Q13季度的一个基因座，在23季度中具有最高的统计学意义。它涉及1型糖尿病与rs1701704的次要等位基因（p = 9.13 x 10（-10）或1.25 [95％CI 1.12-1.40]）。结论 - 我们在12Q13上发现了一个1型糖尿病目的在独立的1型糖尿病患者的队列中，并赋予I型糖尿病的风险可与我们最近报道的16p13基因座。这两个基因座与Wellcome Trust Case-Control联盟的全基因组协会研究确定的两个基因座相同，这是一个平行的独立发现，为GWA方法的有效性提供了进一步的支持。
OBJECTIVE-In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 x 10(-10)) and confirmed in two additional cohorts. Here we describe the results of testing, in these additional cohorts, 23 loci that were next in rank of statistical significance.RESEARCH DESIGN AND METHODS-Two independent cohorts were studied. The Type 1 Diabetes Genetics Consortium replication cohort consisted of 549 families with at least one child diagnosed with diabetes (946 total affected) and DNA from both parents. The Canadian replication cohort consisted of 364 nuclear family trios with one type 1 diabetes-affected offspring and two parents (1,092 individuals).RESULTS-One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves type 1 diabetes association with the minor allele of rs1701704 (P = 9.13 x 10(-10), OR 1.25 [95% CI 1.12-1.40]).CONCLUSIONS-We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type I diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.