Kundu Suman, Kers Jannigje G, Janssens A Cecile J W
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
PLoS One. 2016 Mar 29;11(3):e0152359. doi: 10.1371/journal.pone.0152359. eCollection 2016.
Modeling studies using hypothetical polygenic risk data can be an efficient tool for investigating the effectiveness of downstream applications such as targeting interventions to risk groups to justify whether empirical investigation is warranted. We investigated the assumptions underlying a method that simulates risk data for specific values of the area under the receiver operating characteristic curve (AUC).
The simulation method constructs risk data for a hypothetical population based on the population disease risk, and the odds ratios and frequencies of genetic variants. By systematically varying the parameters, we investigated under what conditions AUC values represent unique ROC curves with unique risk distributions for patients and nonpatients, and to what extend risk data can be simulated for precise values of the AUC.
Using larger number of genetic variants each with a modest effect, we observed that the distributions of estimated risks of patients and nonpatients were similar for various combinations of the odds ratios and frequencies of the risk alleles. Simulated ROC curves overlapped empirical curves with the same AUC.
Polygenic risk data can be effectively and efficiently created using a simulation method. This allows to further investigate the potential applications of stratifying interventions on the basis of polygenic risk.
使用假设的多基因风险数据进行建模研究可能是一种有效的工具，用于调查下游应用的有效性，例如针对风险群体进行干预，以证明是否有必要进行实证研究。我们研究了一种为特定的受试者工作特征曲线下面积（AUC）值模拟风险数据的方法所依据的假设。
该模拟方法基于人群疾病风险、遗传变异的比值比和频率，为一个假设人群构建风险数据。通过系统地改变参数，我们研究了在何种条件下AUC值代表具有患者和非患者独特风险分布的独特ROC曲线，以及可以在多大程度上为AUC的精确值模拟风险数据。
使用大量每个效应适度的遗传变异，我们观察到对于风险等位基因的比值比和频率的各种组合，患者和非患者的估计风险分布相似。模拟的ROC曲线与具有相同AUC的实证曲线重叠。
可以使用模拟方法有效且高效地创建多基因风险数据。这使得能够进一步研究基于多基因风险进行分层干预的潜在应用。
