Properties of Multistage Case - Control Association Study Designs Based on SNP Data for Identifying Disease Susceptibility Genes

A multistage case-control association study is one of the study designs to efficiently identify disease susceptibility genes. The purpose of this study was to clarify the properties of multistage case - control association studies. For this purpose, new programs for n-stage designs (n being an arbitrary integer larger than 1) were developed to calculate statistical powers, positive predictive values (PPVs) and numbers of genotypings of replication - based analysis (RBA) and joint analysis (JA) . Assuming that the numbers of alleles remaining at the final stage or the numbers of genotypings were fixed, the powers and PPVs of RBA and JA in three - stage designs were higher than those indicators in two - stage designs when a proportion of the sample size at the 1st stage (π_<s,1>) was smaller than 0.5. On the other hand, when π_<s,1> j was larger than 0.5, the indicators in the two - stage designs were higher than those in the three - stage designs. This tendency was more remarkable the closer the proportions of sample sizes of the 2nd and 3rd stages were and was more remarkable in JA than in RBA. It may be useful to conduct a prior simulation under various conditions by our programs for multistage designs at the planning stage of a genome - wide association study