Design of case-controls studies with unscreened controls
Design of case-controls studies with unscreened controls
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DOI：
10.1111/j.1529-8817.2005.00175.x
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发表时间：
2005-09-01
影响因子：
1.9
通讯作者：
Craddock, N
中科院分区：
文献类型：
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作者：
Moskvina, V;Holmans, P;Craddock, N
传统上，在遗传病例对照研究中，对照者被筛选以排除有个人病史的受试者。该控制组在检测与疾病相关的基因位点方面具有最佳能力，但需要更多的工作，并且在招募时可能会产生可观的成本。筛查的另一种方法是从一般人群中抽样使用未筛查的对照。这种控制通常是大量和廉价的，但一般来说，有些人可能患有与病例相同的疾病，这将降低检测关联的能力。我们已经量化了这种功率损失的程度，并为获得与固定样本的筛选控制相同的功率所需的未筛选控制的数量产生了数学公式。使用未筛选对照的效果也取决于筛选对照与原始研究设计中指定病例的比例，这也是研究的内容。我们还根据抽样筛查和未筛查对照的相对成本变化，以及基因分型成本，调查了筛查和未筛查方法的成本效益。因此，我们已经确定了一些情况，在这些情况下，使用非筛选对照是筛选对照方法的一种具有成本效益的替代方法，在设计研究时可以考虑使用非筛选对照。在复杂遗传学的许多典型的现实情况中，使用未筛选的对照可能具有成本效益，并且通常可以考虑用于人群患病率K-p < 0.2的疾病。随着基因分型成本的稳步下降和通用“人口控制”的可用性，这种设计可能变得越来越具有成本效益。
Traditionally in genetic case-control studies controls have been screened to exclude subjects with a personal history of illness. This control group has the advantage of optimal power to detect loci involved in illness, but requires more work and may incur substantial cost in recruitment. An alternative approach to screening is to use unscreened controls sampled from the general population. Such controls are generally plentiful and inexpensive, but in general there is a risk that some may have the same disease as the cases, which will reduce power to detect associations. We have quantified the extent of this power loss, and produced mathematical formulae for the number of unscreened controls necessary to achieve the same power as a fixed sample of screened controls. The effect of using unscreened controls will also depend on the ratio of the number of screened controls to cases specified in the original study design, and this is also investigated. We have also investigated the cost-benefits of the screened and unscreened approaches, according to variation in the relative costs of sampling screened and unscreened controls, together with genotyping costs. We have, thus, identified the range of situations in which using unscreened controls is a cost-effective alternative to the screened control method and could be considered when designing a study. In many of the typical, real-world situations in complex genetics, the use of unscreened controls is potentially cost-effective and can, in general, be considered for disorders with population prevalence K-p < 0.2. With the steady reduction in genotyping costs and the availability of common sets of "population controls" this design is likely to become increasingly cost effective.