title: Using Ascertainment for Targeted Resequencing to Increase Power to Identify Causal Variants.
abstract: Researchers continue to use genome-wide association studies (GWAS) to find the genetic markers associated with disease. Recent studies have added to the typical two-stage analysis a third stage that uses targeted resequencing on a randomly selected subset of the cases to detect the causal single-nucleotide polymorphism (SNP). We propose a design for targeted resequencing that increases the power to detect the causal variant. The design features an ascertainment scheme wherein only those cases with the presence of a risk allele are selected for targeted resequencing. We simulated a disease with a single causal SNP to evaluate our method versus a targeted resequencing design using randomly selected individuals. The simulation studies showed that ascertaining individuals for the targeted resequencing can substantially increase the power to detect a causal SNP, without increasing the false-positive rate.
authors.affiliation: Division of Biostatistics, The University of Texas Health Science Center at Houston (UT Health), School of Public Health, Houston, TX 77030.
authors.forename: M D
authors.initials: MD
authors.lastname: Swartz
authors.forename: B
authors.initials: B
authors.lastname: Peng
authors.forename: C
authors.initials: C
authors.lastname: Reyes-Gibby
authors.forename: S
authors.initials: S
authors.lastname: Shete