Using the Estimating Function Bootstrap to Obtain Adjusted p-Values for Quantitative Trait Mapping

• Activity Number: 30
• Type: Contributed
• Date/Time: Sunday, August 1, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Theodore Lystig*+
• Companies: Boehringer Ingelheim Pharmaceuticals, Inc.
• Keywords: Multiple testing ; Permutation tests ; Quantitative trait loci ; Resampling ; Threshold values

Abstract

Genome wide scans for quantitative trait loci (QTL) have traditionally been summarized with plots of logarithm of odds (LOD) scores. A valuable modification is to supplement such plots with an additional vertical axis displaying quantiles of adjusted p-values, and labelling local maxima of the LOD score with location specific adjusted p-values. This provides a visible gradation of genome wide significance for the LOD score curve, instead of the stark dichotomy that a single threshold yields. Adjusted p-values give genome wide signficance of individual LOD scores, and are obtained through a straightforward modification of the familiar algorithm for generating permutation based thresholds. Details are given for how the estimating function bootstrap may be used to reduce drastically the computational burden of the standard permutation approach, under relatively mild assumptions.