Increasing Power to Identify Causal Variants Using Ascertainment for Targeted Resequencing

• Activity Number: 515
• Type: Contributed
• Date/Time: Wednesday, August 3, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Michael Swartz*+ and Cielito Reyes-Gibby and Bo Peng and Sanjay Shete
• Companies: The University of Texas School of Public Health and The University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center
• Keywords: Ascertainment ; Genome-Wide-Association Study ; Causal Polymorphism ; Targeted Resequencing

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.