Tachmazidou Ioanna, De Iorio Maria, Dudbridge Frank
Medical Research Council, Biostatistics Unit, Institute of Public Health, Cambridge, UK.
Hum Hered. 2011;71(1):37-49. doi: 10.1159/000323518. Epub 2011 Mar 10.
The power of genetic association studies is limited by stringent levels of statistical significance. To improve power, Bayes factors (BFs) have been suggested as an alternative measure to the p value, and Storey recently introduced an optimal discovery procedure (ODP) for multiple testing. We aimed to adapt the ODP to genetic case-control studies and to compare its power to p values and asymptotic BFs (ABFs).
We propose estimators of the ODP based on prospective and retrospective likelihoods. We performed simulations based on independent common SNPs and on sequence data including rare variants. Effects of causal SNPs were simulated under various distributions of effect size.
The true ODP is never outperformed, but the estimated ODP has similar power to p values and ABFs. For common SNPs the ODP offers power advantages only in extreme scenarios. However, for rare variants the ODP and ABF detect more associations at low false-positive rates than do p values.
The ODP can provide higher power than p values for genetic case-control studies of common variants. However, as the ABF has similar power to the ODP and is computed more rapidly, it is our currently preferred method.
基因关联研究的效能受到严格统计学显著性水平的限制。为提高效能，有人建议使用贝叶斯因子（BF）作为p值的替代指标，且斯托里最近引入了一种用于多重检验的最优发现程序（ODP）。我们旨在使ODP适用于基因病例对照研究，并将其效能与p值和渐近贝叶斯因子（ABF）进行比较。
我们基于前瞻性和回顾性似然性提出了ODP的估计方法。我们基于独立常见单核苷酸多态性（SNP）和包括罕见变异的序列数据进行了模拟。在效应大小的各种分布下模拟了因果SNP的效应。
真实的ODP从未表现不佳，但估计的ODP与p值和ABF具有相似的效能。对于常见SNP，ODP仅在极端情况下具有效能优势。然而，对于罕见变异，ODP和ABF在低假阳性率时比p值能检测到更多的关联。
对于常见变异的基因病例对照研究，ODP比p值能提供更高的效能。然而，由于ABF与ODP具有相似的效能且计算速度更快，它是我们目前首选的方法。
