We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evaluating rare variants under two-stage design.
- Authors
Li, Qizhai; Pan, Dongdong; Yue, Weihua; Gao, Ying; Yu, Kai
- Abstract
Current genome-wide association studies (GWAS) focusing on relatively common single-nucleotide polymorphisms (SNPs) usually adopt a cost-effective multi-staged design in which a proportion of the total samples are genotyped using a commercial SNP array with a reasonably good coverage of the whole genome at the initial stage, and a list of promising SNPs are further genotyped and evaluated on the remaining samples at the second stage. This staged design in principal can also be used for the study of rare genetic variants at the genome-wide scale, but the statistical methods developed for evaluating the relatively common SNPs under the staged design are not appropriate for rare variants due to the invalidity of large sample theorems. Here, we develop a new statistical framework that aims to evaluate rare variants under two-staged (or multi-staged) design. By extensive computer simulations, we evaluate the empirical type I error rate and power of the proposed procedures. A real example from two recent case-control rheumatoid arthritis genetic association studies is also used to demonstrate the performances of the proposed methods.
- Subjects
HUMAN genome; SINGLE nucleotide polymorphisms; COST effectiveness; GENOTYPE-environment interaction; EMPIRICAL research; COMPUTER simulation; RHEUMATOID arthritis; PERFORMANCE evaluation
- Publication
Journal of Human Genetics, 2012, Vol 57, Issue 6, p352
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1038/jhg.2012.33