A two-stage design is cost-effective for genome-wide association studies (GWAS) testing hundreds of thousands of single nucleotide polymorphisms (SNPs). In this design, each SNP is genotyped in stage 1 using a fraction of case-control samples. Top-ranked SNPs are selected and genotyped in stage 2 using additional samples. A joint analysis, combining statistics from both stages, is applied in th...

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stag...

The problem of selection bias has long been recognized in the analysis of two-stage trials, where promising candidates are selected in stage 1 for confirmatory analysis in stage 2. To efficiently correct for bias, uniformly minimum variance conditionally unbiased estimators (UMVCUEs) have been proposed for a wide variety of trial settings, but where the population parameter estimates are assume...

Pleiotropy is a phenomenon that a single gene inflicts multiple correlated phenotypic effects, often characterized as traits, involving multiple biological systems. We propose a two-stage method to identify pleiotropic effects on multiple longitudinal traits from a family-based data set. The first stage analyzes each longitudinal trait via a three-level mixed-effects model. Random effects at th...

Large-scale genome-wide association studies are increasingly common, due in large part to recent advances in genotyping technology. Despite a dramatic drop in genotyping costs, it is still too expensive to genotype thousands of individuals for hundreds of thousands single-nucleotide polymorphisms (SNPs) for large-scale whole-genome association studies for many researchers. A two-stage design ha...

Because of the high cost of commercial genotyping chip technologies, many investigations have used a two-stage design for genome-wide association studies, using part of the sample for an initial discovery of "promising" SNPs at a less stringent significance level and the remainder in a joint analysis of just these SNPs using custom genotyping. Typical cost savings of about 50% are possible with...