Genomewide transmission/disequilibrium testing--consideration of the genotypic relative risks at disease loci

Abstract

Genomewide association studies are set to become the tool of the future for detection of small-effect genes in complex diseases. It will therefore be necessary to calculate sufficient sample sizes with which to perform them. In this paper I illustrate how to calculate the required number of families for general genotypic relative risks (GRRs). I show the superior sensitivity of the genomewide association study over the 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 association analysis depending on the pattern of the GRRs at the disease locus. In many cases, the comparative numbers of families required under different genetic mechanisms vary by several orders of magnitude. These sometimes dramatic differences have important implications for the determination of the size of the collection of samples prior to analysis and for the types of effects that are likely--and unlikely--to be detected by such an analysis.