Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06511, USA.
Genet Epidemiol. 2013 Jan;37(1):60-8. doi: 10.1002/gepi.21683. Epub 2012 Sep 25.
We consider an Empirical Bayes method to correct for the Winner's Curse phenomenon in genome-wide association studies. Our method utilizes the collective distribution of all odds ratios (ORs) to determine the appropriate correction for a particular single-nucleotide polymorphism (SNP). We can show that this approach is squared error optimal provided that this collective distribution is accurately estimated in its tails. To improve the performance when correcting the OR estimates for the most highly associated SNPs, we develop a second estimator that adaptively combines the Empirical Bayes estimator with a previously considered Conditional Likelihood estimator. The applications of these methods to both simulated and real data suggest improved performance in reducing selection bias.
我们考虑了一种经验贝叶斯方法来纠正全基因组关联研究中的赢家诅咒现象。我们的方法利用所有优势比(OR)的总体分布来确定对特定单核苷酸多态性(SNP)的适当校正。我们可以证明,只要这种总体分布在尾部被准确地估计,这种方法就是均方误差最优的。为了提高对最相关 SNP 的 OR 估计值进行校正时的性能,我们开发了第二种估计器,该估计器自适应地将经验贝叶斯估计器与先前考虑的条件似然估计器相结合。这些方法在模拟和真实数据中的应用表明,在减少选择偏差方面的性能有所提高。