Hagedorn Research Institute, Gentofte, Denmark.
Diabetes. 2010 Jul;59(7):1667-73. doi: 10.2337/db09-1042. Epub 2010 Jan 28.
Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes.
In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants.
When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 x 10(-5), and obese with an OR of 2.62 (1.76-3.92), P = 6.4 x 10(-7), compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67).
The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors.
全基因组关联研究和连锁研究已经确定了 20 个与肥胖和/或相关表型相关的已验证遗传变异。这些变异很常见，它们各自的效应大小在小到中等之间。
在这项研究中，我们研究了这些变异的综合效应及其区分正常体重和超重/肥胖个体的能力。我们应用了接受者操作特征（ROC）曲线，并估计了 ROC 曲线下的面积（AUC）作为区分能力的衡量标准。该分析是在基于人群的 Inter99 队列中进行的，其中有 1725 名正常体重、1519 名超重和 681 名肥胖个体成功地对所有 20 个变异进行了基因分型。
当合并所有变异时，携带超过 22 个风险等位基因的研究参与者中有 10%的人超重的可能性显著增加，优势比为 2.00（1.47-2.72），P=4.0×10（-5），肥胖的优势比为 2.62（1.76-3.92），P=6.4×10（-7），与携带少于 14 个风险等位基因的研究参与者的 10%相比。使用 20 个单核苷酸多态性（SNP），超重和肥胖的判别能力分别确定为 AUC 为 0.53 和 0.58。当将 SNP 数据与肥胖的常规非遗传危险因素结合使用时，超重的判别能力增加到 0.64，肥胖的判别能力增加到 0.69。后者显著高于（P<0.001）非遗传因素单独使用时的 AUC（0.67）。
目前，20 个已验证的常见肥胖变异的判别价值稀疏且太弱，无法用于临床应用，但是，它们可以增加常规非遗传风险因素的判别能力。
