Robust ranks of true associations in genome-wide case-control association studies

Abstract

ABSTRACT : In whole-genome association studies, at the first stage, all markers are tested for association and their test statistics or p-values are ranked. At the second stage, some most significant markers are further analyzed by more powerful statistical methods. This helps reduce the number of hypotheses to be corrected for in multiple testing. Ranks of true associations in genome-wide scans using a single test statistic have been studied. In a case-control design for association, the trend test has been proposed. However, three different trend tests, optimal for the recessive, additive, and dominant models, respectively, are available for each marker. Because the true genetic model is unknown, we rank markers based on multiple test statistics or test statistics robust to model mis-specification. We studied this problem with application to Problem 3 of Genetic Analysis Workshop 15. An independent simulation study was also conducted to further evaluate the proposed procedure.