GENOMEWIDE TRANSMISSION DISEQUILIBRIUM TESTING - CONSIDERATION OF THEGENOTYPIC RELATIVE RISKS AT DISEASE LOCI/

Genomewide association studies are set to become the tool of the futur e for detection of small-effect genes in complex diseases. It will the refore be necessary to calculate sufficient sample sizes with which to perform them. In this paper I illustrate how to calculate the require d number of families for general genotypic relative risks (GRRs). I sh ow the superior sensitivity of the genomewide association study over t he standard genomewide affected-sib-pair linkage analysis, for a range of different underlying GRR patterns. I also illustrate the extent of change in the sample sizes that is necessary for a genomewide associa tion analysis depending on the pattern of the GRRs at the disease locu s. In many cases, the comparative numbers of families required under d ifferent genetic mechanisms vary by several orders of magnitude. These sometimes dramatic differences have important implications for the de termination of the size of the collection of samples prior to analysis and for the types of effects that are likely-and unlikely-to be detec ted by such an analysis.