Empirical Bayes Correction for the Winner's Curse in Genetic Association Studies


Correspondence to: John Ferguson, Yale Center for Statistical Genomics and Proteomics, Suite 503, 300 George Street, New Haven, CT 06511. E-mail: john.ferguson@yale.edu


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.