A weighted-Holm procedure accounting for allele frequencies in genomewide association studies.
In the context of genomewide 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 Bonferroni and sequential Sidak (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 favoring the detection of rare variants with high genetic effects over more frequent ones with lower effects.
Dalmasso
Cyril
C
Université Paris-Sud, Villejuif, France.
Génin
Emmanuelle
E
Trégouet
David-Alexandre
DA
D000483:Alleles; D003324:Coronary Artery Disease / Q000235:genetics; D003627:Data Interpretation, Statistical; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D009369:Neoplasms / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic