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A Note on the Efficiencies of Sampling Strategies in Two‐Stage Bayesian Regional Fine Mapping of a Quantitative Trait
Author(s) -
Chen Zhijian,
Craiu Radu V.,
Bull Shelley B.
Publication year - 2014
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21845
Subject(s) - genome wide association study , bayesian probability , genetic association , inference , computer science , bayesian inference , quantitative trait locus , trait , snp , sample size determination , snp genotyping , tag snp , posterior probability , computational biology , biology , statistics , genotyping , single nucleotide polymorphism , genetics , mathematics , artificial intelligence , genotype , gene , programming language
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.