摘要：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.
关键词：ascertainment; genome-wide association study; causal polymorphism; targeted resequencing
