A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3.
A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3.
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人类1型糖尿病易感性基因座图与染色体21q22.3。
DOI：
10.2337/db08-0753
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发表时间：
2008-10
期刊：
影响因子：
7.7
通讯作者：
Type 1 Diabetes Genetics Consortium
中科院分区：
文献类型：
--
作者：
Concannon P;Onengut-Gumuscu S;Todd JA;Smyth DJ;Pociot F;Bergholdt R;Akolkar B;Erlich HA;Hilner JE;Julier C;Morahan G;Nerup J;Nierras CR;Chen WM;Rich SS;Type 1 Diabetes Genetics Consortium
目的 - 1型糖尿病遗传联盟（T1DGC）已组装并基因分型，以绘制与1型糖尿病相关的基因组区域，我们在当前研究中测试了与1型糖尿病相关的证据。利用全基因组链接扫描数据和基于家庭的关联方法。
研究设计和方法 - 由6,090个单一核苷酸多态性（SNP）进行了2,496个多个糖尿病的多个家庭。两组独立样本的分析：2,214个受父母影响的儿童家庭和一个7,721的小组案例和9,679个对照对象。
结果 - 三个SNP与先前确定的1型糖尿病的1型糖尿病最密切相关。在两个独立的样本集中获得了染色体21q22.3的UBASH3A基因座的第六个内含子。糖尿病（优势比[OR] 1.06 [95％CI 1.00-1.11]; P = 0.023）和病例和对照对象（1.14 [1.09–1.19]; P = 7.5×10-8）。
结论 - 此处报道的T1DGC 6K SNP扫描和后续研究证实，先前报道了INS，IFIH1和KIAA0350的1型糖尿病关联，并确定了UBASH3A基因座中染色体21q22.3的其他疾病协会（OR 1.10 [95％CI CI [95％CI CI） 1.07–1.13]; p = 4.4×10-12）。基因分型和1型糖尿病的功能研究。
OBJECTIVE— The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled and genotyped a large collection of multiplex families for the purpose of mapping genomic regions linked to type 1 diabetes. In the current study, we tested for evidence of loci associated with type 1 diabetes utilizing genome-wide linkage scan data and family-based association methods. RESEARCH DESIGN AND METHODS— A total of 2,496 multiplex families with type 1 diabetes were genotyped with a panel of 6,090 single nucleotide polymorphisms (SNPs). Evidence of association to disease was evaluated by the pedigree disequilibrium test. Significant results were followed up by genotyping and analyses in two independent sets of samples: 2,214 parent-affected child trio families and a panel of 7,721 case and 9,679 control subjects. RESULTS— Three of the SNPs most strongly associated with type 1 diabetes localized to previously identified type 1 diabetes risk loci: INS, IFIH1, and KIAA0350. A fourth strongly associated SNP, rs876498 (P = 1.0 × 10−4), occurred in the sixth intron of the UBASH3A locus at chromosome 21q22.3. Support for this disease association was obtained in two additional independent sample sets: families with type 1 diabetes (odds ratio [OR] 1.06 [95% CI 1.00–1.11]; P = 0.023) and case and control subjects (1.14 [1.09–1.19]; P = 7.5 × 10−8). CONCLUSIONS— The T1DGC 6K SNP scan and follow-up studies reported here confirm previously reported type 1 diabetes associations at INS, IFIH1, and KIAA0350 and identify an additional disease association on chromosome 21q22.3 in the UBASH3A locus (OR 1.10 [95% CI 1.07–1.13]; P = 4.4 × 10−12). This gene and its flanking regions are now validated targets for further resequencing, genotyping, and functional studies in type 1 diabetes.
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