Belsky Daniel W, Moffitt Terrie E, Sugden Karen, Williams Benjamin, Houts Renate, McCarthy Jeanette, Caspi Avshalom
Department of Health Policy & Management , University of North Carolina , Chapel Hill , NC, USA.
Biodemography Soc Biol. 2013;59(1):85-100. doi: 10.1080/19485565.2013.774628.
Multi-locus profiles of genetic risk, so-called "genetic risk scores," can be used to translate discoveries from genome-wide association studies into tools for population health research. We developed a genetic risk score for obesity from results of 16 published genome-wide association studies of obesity phenotypes in European-descent samples. We then evaluated this genetic risk score using data from the Atherosclerosis Risk in Communities (ARIC) cohort GWAS sample (N = 10,745, 55% female, 77% white, 23% African American). Our 32-locus GRS was a statistically significant predictor of body mass index (BMI) and obesity among ARIC whites [for BMI, r = 0.13, p<1 × 10(-30); for obesity, area under the receiver operating characteristic curve (AUC) = 0.57 (95% CI 0.55-0.58)]. The GRS predicted differences in obesity risk net of demographic, geographic, and socioeconomic information. The GRS performed less well among African Americans. The genetic risk score we derived from GWAS provides a molecular measurement of genetic predisposition to elevated BMI and obesity.[Supplemental materials are available for this article. Go to the publisher's online edition of Biodemography and Social Biology for the following resource: Supplement to Development & Evaluation of a Genetic Risk Score for Obesity.].
多基因座遗传风险概况，即所谓的“遗传风险评分”，可用于将全基因组关联研究的发现转化为人群健康研究工具。我们根据16项已发表的针对欧洲裔样本肥胖表型的全基因组关联研究结果，开发了一种肥胖遗传风险评分。然后，我们使用社区动脉粥样硬化风险（ARIC）队列全基因组关联研究样本（N = 10745，55%为女性，77%为白人，23%为非裔美国人）的数据对该遗传风险评分进行了评估。我们的32基因座遗传风险评分是ARIC白人中体重指数（BMI）和肥胖的统计学显著预测指标[对于BMI，r = 0.13，p<1×10(-30)；对于肥胖，受试者工作特征曲线下面积（AUC）= 0.57（95%置信区间0.55 - 0.58）]。该遗传风险评分预测了排除人口统计学、地理和社会经济信息后的肥胖风险差异。该遗传风险评分在非裔美国人中的表现较差。我们从全基因组关联研究中得出的遗传风险评分为BMI升高和肥胖的遗传易感性提供了一种分子测量方法。[本文提供补充材料。请前往出版商的《生物人口学与社会生物学》在线版获取以下资源：肥胖遗传风险评分的开发与评估补充材料。]
