Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association.

ABSTRACT: To date, gene-based rare variant testing approaches have focused on aggregating information across sets of variants to maximize statistical power in identifying genes showing significant association with diseases. Beyond identifying genes that are associated with diseases, the identification of causal variant(s) in those genes and estimation of their effect is crucial for planning replication studies and characterizing the genetic architecture of the locus. However, we illustrate that straightforward single-marker association statistics can suffer from substantial bias introduced by conditioning on gene-based test significance, due to the phenomenon often referred to as "winner's curse." We illustrate the ramifications of this bias on variant effect size estimation and variant prioritizati

SUBMITTER: Grinde KE 

PROVIDER: S-EPMC5603735 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature