title: One-stage design is empirically more powerful than two-stage design for family-based genome-wide association studies.
abstract: Finding a genetic marker associated with a trait is a classic problem in human genetics. Recently, two-stage approaches have gained popularity in marker-trait association studies, in part because researchers hope to reduce the multiple testing problem by testing fewer markers in the final stage. We compared one two-stage family-based approach to an analogous single-stage method, calculating the empirical type I error rates and power for both methods using fully simulated data sets modeled on nuclear families with rheumatoid arthritis, and data sets of real single-nucleotide polymorphism genotypes from Centre d'Etude du Polymorphisme Humain pedigrees with simulated traits. In these analyses performed in the absence of population stratification, the single-stage method was consistently more powerful than the two-stage method for a given type I error rate. To explore the sources of this difference, we performed a case study comparing the individual steps of two-stage designs, the two-stage design itself, and the analogous one-stage design.
authors.affiliation: Department of Genome Sciences, University of Washington, 1705 Northeast Pacific Street #K-357, Box 357730, Seattle, Washington 98195, USA. rrohlfs@u.washington.edu
authors.forename: Rori V
authors.initials: RV
authors.lastname: Rohlfs
authors.forename: Chelsea
authors.initials: C
authors.lastname: Taylor
authors.forename: Lucia
authors.initials: L
authors.lastname: Mirea
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
authors.forename: Mary
authors.initials: M
authors.lastname: Corey
authors.forename: Amy D
authors.initials: AD
authors.lastname: Anderson