A Note on the Efficiencies of Sampling Strategies in Two‐Stage Bayesian Regional Fine Mapping of a Quantitative Trait. Issue 7 (1st August 2014)

• Record Type: Journal Article
• Authors: Chen, Zhijian; Craiu, Radu V.; Bull, Shelley B.
• Is Part Of: Genetic epidemiology. Volume 38:Issue 7(2014)
• Page Start: 599
• Page End: 609
• Publication Date: 2014-08-01
• Subjects: Genetic epidemiology -- Periodicals; Heredity -- Periodicals; Medical geography -- Periodicals; 614
• DOI: 10.1002/gepi.21845
• Languages: English
• ISSNs: 0741-0395

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>In focused studies designed to follow up associations detected in a genome‐wide association study (GWAS), investigators can proceed to fine‐map a genomic region by targeted sequencing or dense genotyping of all variants in the region, aiming to identify a functional sequence variant. For the analysis of a quantitative trait, we consider a Bayesian approach to fine‐mapping study design that incorporates stratification according to a promising GWAS tag SNP in the same region. Improved cost‐efficiency can be achieved when the fine‐mapping phase incorporates a two‐stage design, with identification of a smaller set of more promising variants in a subsample taken in stage 1, followed by their evaluation in an independent stage 2 subsample. To avoid the potential negative impact of genetic model misspecification on inference we incorporate genetic model selection based on posterior probabilities for each competing model. Our simulation study shows that, compared to simple random sampling that ignores genetic information from GWAS, tag‐SNP‐based stratified sample allocation methods reduce the number of variants continuing to stage 2 and are more likely to promote the functional sequence variant into confirmation studies.</p> </abstract>