Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals
Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals
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DOI：
10.1007/s00125-009-1397-5
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发表时间：
2009-08-01
期刊：
影响因子：
8.2
通讯作者：
Maeda, S.
中科院分区：
文献类型：
--
作者：
Omori, S.;Tanaka, Y.;Maeda, S.
通过对欧洲人群全基因组关联研究（GWAS）的荟萃分析，已经确定了2型糖尿病的其他易感基因座。为了进一步研究这些新基因座的作用，我们在三个独立的日本人群中进行了一项重复性研究，以确定这些单核苷酸多态性（SNP）基因座与该疾病的关联。我们对欧洲GWAS荟萃分析第2阶段出现的11个SNP中的7个进行了基因分型（JAZF 1中的rs 864745，CDC 123/CAMK 1D附近的rs 12779790，TSPAN 8/LGR 5附近的rs7961581，ADAMTS 9附近的rs 4607103，NOTCH 2中的rs 10923931，DCD附近的rs 1153188和VEGFA附近的rs 9472138）（第一组，1，630名2型糖尿病患者对1，064名对照;第二组，1，272名2型糖尿病患者对856名对照;第三组，486名2型糖尿病患者对936名对照）。采用logistic回归分析，调整年龄、性别和BMI，对每个人群中SNP位点的关联性进行分析，并通过荟萃分析对数据进行评估，对三项病例对照研究的荟萃分析确定JAZF 1中rs 864745与2型糖尿病的名义关联（OR 1.148，95% CI 1.034-1.275，p = 0.0098，校正p = 0.069）。其他基因座的相关性未达到统计学显著水平（名义p > 0.05）。从这些结果来看，这7个基因座在日本人群中对2型糖尿病易感性的贡献被认为是次要的，如果它们存在的话。
Additional susceptibility loci for type 2 diabetes have been identified by a meta-analysis of genome-wide association studies (GWASs) in European populations. To examine further the roles of these new loci, we performed a replication study for the association of these single-nucleotide polymorphism (SNP) loci with the disease in three independent Japanese populations.We genotyped seven of the 11 SNPs that emerged in stage 2 of the meta-analysis for European GWASs (rs864745 in JAZF1, rs12779790 near CDC123/CAMK1D, rs7961581 near TSPAN8/LGR5, rs4607103 near ADAMTS9, rs10923931 in NOTCH2, rs1153188 near DCD and rs9472138 near VEGFA) for three independent Japanese populations (first set, 1,630 type 2 diabetes patients vs 1,064 controls; second set, 1,272 type 2 diabetes patients vs 856 controls; third set, 486 type 2 diabetes patients vs 936 controls) using a TaqMan assay. The association of the SNP loci in each population was analysed using a logistic regression analysis, adjusting for age, sex and BMI, and the data were evaluated by a meta-analysis.A meta-analysis for the three case-control studies identified a nominal association of rs864745 in JAZF1 with type 2 diabetes (OR 1.148, 95% CI 1.034-1.275, p = 0.0098, corrected p = 0.069). The association of other loci did not reach statistically significant levels (nominal p > 0.05).From these results the contribution of these seven loci in conferring susceptibility to type 2 diabetes is considered minor in the Japanese population, if they are present.