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首页> 外文期刊>Diabetes >Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish Evidence for Replication From Diabetes-Related Quantitative Traits and From Independent Populations
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Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish Evidence for Replication From Diabetes-Related Quantitative Traits and From Independent Populations

机译：从旧的全基因组证据的全基因组扫描中，从糖尿病相关的定量特征和独立人群中复制的全基因组扫描识别2型糖尿病的新候选基因。

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OBJECTIVE-We sought to identify type 2 diabetes susceptibility genes through a genome-wide association scan (GWAS) in the Amish. RESEARCH DESIGN AND METHODS-DNA from 124 type 2 diabetic case subjects and 295 control subjects with normal glucose tolerance were genotyped on the Affymetrix 100K single nucleotide polymorphism (SNP) array. A total of 82,485 SNPs were tested for association with type 2 diabetes. Type 2 diabetes-associated SNPs were further prioritized by the following: 1) associations with 5 oral glucose tolerance test (OGTT) traits in 427 nondiabetic Amish subjects, and 2) in silico replication from three independent 100L SNP GWASs (Framingham Heart Study Caucasians, Pima Indians, and Mexican Americans) and a 500K GWAS in Scandinavians. RESULTS- The strongest association (P = 1.07 × 10~(-5)) was for rs2237457, which is located in growth factor receptor-bound protein 10 (Grb10), an adaptor protein that regulate insulin receptor signaling. rs2237457 was also strongly associated with OGTT glucose area under the curve in nondiabetic subjects (P = 0.001). Of the 1,093 SNPs associated with type 2 diabetes at P < 0.01, 67 SNPs demonstrated associations with at least one OGTT trait in nondiabetic individuals; 80 SNPs were nominally associated with type 2 diabetes in one of the three independent 100K GWASs, 3 SNPs (rs2540317 in MFSD9, rsl0515353 on chromosome 5, and rs2242400 in BCAT1 were associated with type 2 diabetes in more than one population), and 11 SNPs were nominally associated with type 2 diabetes in Scandinavians. One type 2 diabetes-associated SNP (rs3845971, located in FHIT) showed replication with OGTT traits and also in another population. CONCLUSIONS-Our GWAS of type 2 diabetes identified several gene variants associated with type 2 diabetes, some of which are worthy of further study.
机译：目的-我们试图通过阿米什语中的全基因组关联扫描（GWAS）识别2型糖尿病易感性基因。研究设计和方法-在Affymetrix 100K单核苷酸多态性（SNP）阵列上对来自124位2型糖尿病病例受试者和295名糖耐量正常的对照组受试者的DNA进行基因分型。测试了总共82,485个SNP与2型糖尿病的关联。与2型糖尿病相关的SNP的优先级如下：1）在427名非糖尿病阿米什人中具有5种口服葡萄糖耐量测试（OGTT）性状的关联，以及2）从三个独立的100L SNP GWAS进行计算机复制（Framingham Heart Study白种人，皮马印第安人和墨西哥裔美国人）和斯堪的纳维亚人的500K GWAS。结果-rs2237457的关联最强（P = 1.07×10〜（-5）），其位于生长因子受体结合蛋白10（Grb10）中，后者是调节胰岛素受体信号传导的衔接蛋白。在非糖尿病受试者中，rs2237457也与曲线下的OGTT葡萄糖面积密切相关（P = 0.001）。在P <0.01时，与2型糖尿病相关的1,093个SNP中，有67个SNP在非糖尿病个体中表现出至少与一种OGTT性状相关。在三个独立的100K GWAS中，有80个SNP名义上与2型糖尿病相关，三个SNP（MFSD9中的rs2540317、5号染色体上的rs1055153和BCAT1中的rs2242400与一个以上人群中的2型糖尿病相关）和11个SNP。斯堪的纳维亚人名义上与2型糖尿病相关。一个与2型糖尿病相关的SNP（位于FHIT中的rs3845971）显示出具有OGTT性状的复制，也出现在另一个人群中。结论-我们的2型糖尿病GWAS确定了与2型糖尿病相关的几种基因变异，其中一些值得进一步研究。

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