Aspects of the design and analysis of high-dimensional SNP studies for disease risk estimation
Aspects of the design and analysis of high-dimensional SNP studies for disease risk estimation
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DOI：
10.1093/biostatistics/kxj020
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发表时间：
2006-07-01
期刊：
影响因子：
2.1
通讯作者：
Qi, Lihong
中科院分区：
文献类型：
--
作者：
Prentice, Ross L.;Qi, Lihong
高维单核苷酸多态性（SNP）流行病学关联研究的准备状态进行了描述，作为背景的病例对照研究设计和分析的统计方面的讨论。特别是，多阶段设计可以发挥的重要作用，在消除假阳性协会和控制研究成本将被注意到。此外，将详细讨论在早期设计阶段使用合并DNA以进一步降低成本的权衡。将提出一个比值比的方法，与一个简单的经验方差估计，根据不同的病例和对照池的对数比值比估计之间的比较，结合使用合并的DNA SNP等位基因的疾病风险。模拟研究将提出评估中等样本量的性质，这样的多级设计和估计程序。正在进行的三个阶段的研究，在妇女健康倡议的设计，涉及250 000 SNP的冠心病，中风和乳腺癌的风险将提供说明，并将被用来激励选择的模拟配置。
The state of readiness for high-dimensional single nucleotide polymorphism (SNP) epidemiologic association studies is described, as background for a discussion of statistical aspects of case-control study design and analysis. Specifically, the important role that multistage designs can play in the elimination of false-positive associations and in the control of study costs will be noted. Also, the trade-offs associated with using pooled DNA at early design stages for additional important cost reductions will be discussed in some detail. An odds ratio approach to relating SNP alleles to disease risk using pooled DNA will be proposed, in conjunction with a simple empirical variance estimator, based on comparisons among log-odds ratio estimators from distinct pairs of case and control pools. Simulation studies will be presented to evaluate the moderate sample size properties of such multistage designs and estimation procedures. The design of an ongoing three-stage study in the Women's Health Initiative to relate 250 000 SNPs to the risk of coronary heart disease, stroke, and breast cancer will provide illustration, and will be used to motivate the choice of simulation configurations.