title: Application of the stepwise focusing method to optimize the cost-effectiveness of genome-wide association studies with limited research budgets for genotyping and phenotyping.
abstract: The recent cataloguing of a large number of SNPs enables us to perform genome-wide association studies for detecting common genetic variants associated with disease. Such studies, however, generally have limited research budgets for genotyping and phenotyping. It is therefore necessary to optimize the study design by determining the most cost-effective numbers of SNPs and individuals to analyze. In this report we applied the stepwise focusing method, with two-stage design, developed by Satagopan et al. (2002) and Saito & Kamatani (2002), to optimize the cost-effectiveness of a genome-wide direct association study using a transmission/disequilibrium test (TDT). The stepwise focusing method consists of two steps: a large number of SNPs are examined in the first focusing step, and then all the SNPs showing a significant P-value are tested again using a larger set of individuals in the second focusing step. In the framework of optimization, the numbers of SNPs and families and the significance levels in the first and second steps were regarded as variables to be considered. Our results showed that the stepwise focusing method achieves a distinct gain of power compared to a conventional method with the same research budget.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. juno-tky@umin.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
authors.forename: A G
authors.initials: AG
authors.lastname: Clark
mesh_terms: D003363:Cost Control; D003362:Cost-Benefit Analysis; D023281:Genomics / Q000191:economics*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D012109:Research Support as Topic