title: Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes.
abstract: A two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1-754 Chuo-ku, Asahimachi-dori, Niigata, 951-8520, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1-754 Chuo-ku, Asahimachi-dori, Niigata, 951-8520, Japan. akazawa@med.niigata-u.ac.jp.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1-754 Chuo-ku, Asahimachi-dori, Niigata, 951-8520, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Toyabe
authors.affiliation: Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresources, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Miyashita
authors.affiliation: Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresources, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1-754 Chuo-ku, Asahimachi-dori, Niigata, 951-8520, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D016022:Case-Control Studies; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012107:Research Design; D018401:Sample Size