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B1192
Title: Controlling the rate of GWAS false discoveries Authors:  Malgorzata Bogdan - Lund University (Sweden) [presenting]
Damian Brzyski - Jagiellonian University (Poland)
Christine Peterson - Stanford University (United States)
Piotr Sobczyk - Politechnika Wroclawska (Poland)
Emmanuel Candes - Stanford (United States)
Chiara Sabatti - Stanford University (United States)
Abstract: With the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. The nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on pre-screening to identify the level of resolution of distinct hypotheses. We show how FDR controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS.