Genetics. Published Articles Ahead of Print: August 24, 2008, Copyright © 2008
doi:10.1534/genetics.108.089839


A more recent version of this article appeared on September 1, 2008.


NOTE

A Weighted-Holm Procedure accounting for allele frequencies in Genome-Wide Association Studies

1 Université Paris-Sud
2 INSERM

* To whom correspondence should be addressed. E-mail: tregouet{at}chups.jussieu.fr.

Submitted on April 5, 2008
Revised on May 28, 2008
Accepted on 27 June 2008


Abstract

In the context of genome-wide association studies where hundreds of thousand of polymorphisms are tested, stringent thresholds on the raw association test p-values are generally used to limit false positive results. Instead of using thresholds based on raw p-values as in Bonferronni and SidakSD corrections, we propose here to use a Weighted-Holm procedure with weights depending on allele frequency of the polymorphisms. This method is shown to substantially improve the power to detect associations, in particular by favouring the detection of rare variants with high genetic effects over more frequent ones with lower effects.

Key Words: GWAS, SNP, association study, multiple testing, p-value