A simple correction for multiple comparisons in interval mapping genome scans

Abstract

Several approaches have been proposed to correct point-wise significance thresholds used in interval-mapping genome scans. A method for significance threshold correction based on the Bonferroni test is presented. This test involves calculating the effective number of independent comparisons performed in a genome scan from the variance of the eigenvalues of the observed marker correlation matrix. The more highly correlated the markers, the higher the variance of the eigenvalues and the lower the number of independent tests performed on a chromosome. This approach was evaluated by mapping 1000 normally distributed phenotypes along chromosomes of varying length and marker density in a population size of 500. Experiment-wise significance thresholds obtained from the simulation are compared to those calculated using the Bonferroni criterion and the newly developed measure of the effective number of independent tests in a genome scan. The Bonferroni calculation produced significance thresholds very similar to those obtained by simulation. The threshold levels for both Bonferroni and simulation analysis depended strongly on the marker density and size of chromosomes. There was a slight bias of about 1% in the thresholds obtained at the 5% and 10% point-wise significance levels. The method introduced here provides a relatively simple correction for multiple comparisons that can be easily calculated using standard statistics packages.