Cumulative Effect of Common Genetic Variants Predicts Incident Type 2 Diabetes: A Study of 21,183 Subjects from Three Large Prospective Cohorts
Cumulative Effect of Common Genetic Variants Predicts Incident Type 2 Diabetes: A Study of 21,183 Subjects from Three Large Prospective Cohorts
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常见遗传变异的累积效应可预测 2 型糖尿病的发生：对来自三个大型前瞻性队列的 21,183 名受试者进行的研究
DOI：
10.4172/2161-1165.1000108
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Jinying Zhao
中科院分区：
文献类型：
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作者：
Jingyun Yang;Jinying Zhao
最近的全基因组关联研究 (GWAS) 及其荟萃分析已经确定了与 2 型糖尿病 (T2D) 相关的多个遗传位点。除了 TCF7L2 基因变异对糖尿病风险影响不大之外，迄今为止发现的大多数基因变异与糖尿病的关联性较弱。多种变异的组合可能对疾病风险产生更大的影响并改善风险预测。在这项研究中，我们重点关注在之前的 GWAS 中得到可靠复制的 SNP，并且还在来自三个大型前瞻性队列的 21,183 名参与者的大样本中进行了基因分型，包括社区动脉粥样硬化风险 (ARIC) 研究、弗雷明汉后代研究 (FOS) 和动脉粥样硬化多种族研究 (MESA)。其中，我们能够成功确认 12 个 SNP 与这两个队列中基线流行的 T2D 的关联。使用这 12 个风险变异构建基因型风险评分 (GRS)，以检查 GRS 是否可以预测糖尿病的发生。在一项综合荟萃分析中，在调整年龄、性别、种族、吸烟、体重指数（BMI）、血脂（HDL和LDL）和收缩压后，与GRS最低三分位数的受试者相比，GRS最高三分位数的受试者发生T2D的风险增加了1.62倍（95% CI，1.08–2.44，P=1.5×10−14）。此外，GRS 显着改善了 T2D 的风险预测和重新分类，超越了已知的风险因素。
Recent genome-wide association studies (GWAS) and their meta-analyses have identified multiple genetic loci that are associated with type 2 diabetes (T2D). Except for variants in the TCF7L2 gene which had a modest effect on diabetic risk, most genetic variants identified so far have only a weak association with diabetes. It is possible that the combination of multiple variants may have a larger effect on disease risk and improve risk prediction. In this study, we focus on SNPs that had been robustly replicated in previous GWAS and were also genotyped in a large sample of 21,183 participants from three large prospective cohorts, including Atherosclerosis Risk in Communities (ARIC) Study, Framingham Offspring Study (FOS) and Multi-Ethnic Study of Atherosclerosis (MESA). Among these, we were able to successfully confirm the associations of 12 SNPs with baseline prevalent T2D in these two cohorts. A genotype risk score (GRS) using these12 risk variants was constructed to examine whether GRS predicts incident diabetes. In a combined meta-analysis, subjects in the highest tertile of GRS had a 1.62-fold increased risk of incident T2D (95% CI, 1.08–2.44, P=1.5×10−14) compared to those in the lowest tertile of GRS after adjustment for age, sex, race, smoking, body mass index (BMI), lipids (HDL and LDL) and systolic blood pressure. Moreover, GRS significantly improves risk prediction and reclassification in T2D beyond known risk factors.
DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
S. Thomas;L. Scott;K. Mohlke;L. Bonnycastle;C. Willer;Yun Li;W. Duren;M. Erdos;H. Stringham
通讯作者：
S. Thomas;L. Scott;K. Mohlke;L. Bonnycastle;C. Willer;Yun Li;W. Duren;M. Erdos;H. Stringham