Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, 294 Tai-Yuan Road, Shanghai 200031, People's Republic of China.
Diabetologia. 2010 Oct;53(10):2163-6. doi: 10.1007/s00125-010-1826-5. Epub 2010 Jun 17.
AIMS/HYPOTHESIS: The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese.
We genotyped 17 variants in 17 loci in a population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve.
The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12-1.23, p = 1.3 x 10(-12)) and 1.12 (95% CI 1.09-1.16, p = 7.5 x 10(-14)), respectively. Compared with participants with GRS < or =11.0 (7.63%), those with GRS > or =19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49-8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function (p = 8.4 x 10(-10)). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA(1c) levels (p = 0.04 and p = 0.03 for interaction, respectively). Discrimination of diabetes risk was improved (p < 0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added.
CONCLUSIONS/INTERPRETATION: In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes.
目的/假设：全基因组关联研究的最新进展极大地加速了 2 型糖尿病位点的鉴定。我们旨在研究多种遗传变异的单独或与传统危险因素联合作用对汉族人群 2 型糖尿病和糖尿病相关特征的影响。
我们对一个基于人群的汉族队列中的 17 个位点的 17 个变异进行了基因分型，该队列包括 3210 个无关个体。基于这些变异计算了遗传风险评分（GRS）。通过接受者操作特征曲线下的面积来评估判别能力。
每个 GRS 点（每个风险等位基因）的 2 型糖尿病和高血糖的比值比为 1.18（95%CI 1.12-1.23，p=1.3×10(-12))和 1.12（95%CI 1.09-1.16，p=7.5×10(-14))。与 GRS<或=11.0（7.63%）的参与者相比，GRS>或=19.0（8.87%）的参与者患 2 型糖尿病的风险高 4.58 倍（95%CI 2.49-8.42）。GRS 还与通过 HOMA-β细胞功能估计的β细胞功能降低显著相关（p=8.4×10(-10))。此外，我们观察到 GRS 与 BMI 之间在空腹血糖和 HbA(1c)水平上存在显著的交互作用（交互作用 p 值分别为 0.04 和 0.03）。当 GRS 加入包括临床危险因素的模型时，糖尿病风险的判别得到改善（p<0.001）。GRS 和常规临床危险因素单独的 AUC 分别为 0.62 和 0.77，当加入 GRS 时为 0.79。
结论/解释：在这个汉族人群中，17 个联合变异的 GRS 适度但显著地提高了对 2 型糖尿病的传统危险因素的判别能力。
