Statistics and Its Interface

Volume 4 (2011)

Number 3

Using ascertainment for targeted resequencing to increase power to identify causal variants

Pages: 285 – 294

DOI: http://dx.doi.org/10.4310/SII.2011.v4.n3.a3

Authors

B. Peng (Department of Epidemiology, The University of Texas, Houston, Texas, U.S.A.)

C. Reyes-Gibby (Department of Epidemiology, The University of Texas, Houston, Texas, U.S.A.)

S. Shete (Department of Epidemiology, The University of Texas, Houston, Texas, U.S.A.)

M. D. Swartz (Division of Biostatistics, The University of Texas Health Science Center, Houston, Texas, U.S.A.)

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.

Keywords

ascertainment, genome-wide association study, causal polymorphism, targeted resequencing

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