Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
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DOI：
10.2337/db08-0425
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发表时间：
2008-11
期刊：
影响因子：
7.7
通讯作者：
Janssens AC
中科院分区：
文献类型：
--
作者：
van Hoek M;Dehghan A;Witteman JC;van Duijn CM;Uitterlinden AG;Oostra BA;Hofman A;Sijbrands EJ;Janssens AC
目的：基于基因检测的2型糖尿病预测可能提高对高危人群的识别。全基因组关联（GWA）研究发现了与2型糖尿病相关的多种新的遗传变异。基因检测对一般人群2型糖尿病的预测价值尚不清楚。研究设计和方法：我们在鹿特丹研究中调查了最近关于2型糖尿病的GWA研究中的18个多态性，鹿特丹研究是一项前瞻性、基于人群的研究，研究对象为55岁及以上的同质高加索人（基因分型受试者，n = 6544；流行病例，n = 686；随访期间的事件病例，n = 601；平均随访10.6年）。使用logistic和Cox回归分析对这些多态性的预测价值以及临床特征进行单独检验。用受试者工作特征曲线下面积（auc）评价预测模型的判别精度。结果：在18个多态性中，ADAMTS9、CDKAL1、CDKN2A/B-rs1412829、FTO、IGF2BP2、JAZF1、SLC30A8、TCF7L2和WFS1变异与2型糖尿病风险相关。基于遗传多态性预测的AUC为0.60 (95% CI 0.57-0.63)；年龄、性别和BMI为0.66 (0.63-0.68)；遗传多态性与临床特征的比值为0.68（0.66 ~ 0.71）。结论：在一项基于人群的研究中，我们发现18个确定的遗传风险变异中有9个与2型糖尿病相关。在以人群为基础的水平上，结合遗传变异对未来2型糖尿病的预测价值较低。除临床特征外，遗传多态性仅略微提高了2型糖尿病的预测。
OBJECTIVE—Prediction of type 2 diabetes based on genetic testing might improve identification of high-risk subjects. Genome-wide association (GWA) studies identified multiple new genetic variants that associate with type 2 diabetes. The predictive value of genetic testing for prediction of type 2 diabetes in the general population is unclear. RESEARCH DESIGN AND METHODS—We investigated 18 polymorphisms from recent GWA studies on type 2 diabetes in the Rotterdam Study, a prospective, population-based study among homogeneous Caucasian individuals of 55 years and older (genotyped subjects, n = 6,544; prevalent cases, n = 686; incident cases during follow-up, n = 601; mean follow-up 10.6 years). The predictive value of these polymorphisms was examined alone and in addition to clinical characteristics using logistic and Cox regression analyses. The discriminative accuracy of the prediction models was assessed by the area under the receiver operating characteristic curves (AUCs). RESULTS—Of the 18 polymorphisms, the ADAMTS9, CDKAL1, CDKN2A/B-rs1412829, FTO, IGF2BP2, JAZF1, SLC30A8, TCF7L2, and WFS1 variants were associated with type 2 diabetes risk in our population. The AUC was 0.60 (95% CI 0.57–0.63) for prediction based on the genetic polymorphisms; 0.66 (0.63–0.68) for age, sex, and BMI; and 0.68 (0.66–0.71) for the genetic polymorphisms and clinical characteristics combined. CONCLUSIONS—We showed that 9 of 18 well-established genetic risk variants were associated with type 2 diabetes in a population-based study. Combining genetic variants has low predictive value for future type 2 diabetes at a population-based level. The genetic polymorphisms only marginally improved the prediction of type 2 diabetes beyond clinical characteristics.