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Bayesian variable selection using partially observed categorical prior information in fine-mapping association studies

Lookup NU author(s): Abdullah Alenezi, Dr Wei-Yu Lin

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Abstract

© 2019 Wiley Periodicals, Inc.Several methods have been proposed to allow functional genomic information to inform prior distributions in Bayesian fine-mapping case–control association studies. None of these methods allow the inclusion of partially observed functional genomic information. We use functional significance (FS) scores that combine information across multiple bioinformatics sources to inform our effect size prior distributions. These scores are not available for all single-nucleotide polymorphisms (SNPs) but by partitioning SNPs into naturally occurring FS score groups, we show how missing FS scores can easily be accommodated via finite mixtures of elicited priors. Most current approaches adopt a formal Bayesian variable selection approach and either limit the number of causal SNPs allowed or use approximations to avoid the need to explore the vast parameter space. We focus instead on achieving differential shrinkage of the effect sizes through prior scale mixtures of normals and use marginal posterior probability intervals to select candidate causal SNPs. We show via a simulation study how this approach can improve localisation of the causal SNPs compared to existing mutli-SNP fine-mapping methods. We also apply our approach to fine-mapping a region around the CASP8 gene using the iCOGS consortium breast cancer SNP data.


Publication metadata

Author(s): Alenazi AA, Cox A, Juarez M, Lin W-Y, Walters K

Publication type: Article

Publication status: Published

Journal: Genetic Epidemiology

Year: 2019

Volume: 43

Issue: 6

Pages: 690-703

Print publication date: 08/08/2019

Online publication date: 12/07/2019

Acceptance date: 07/05/2019

ISSN (print): 0741-0395

ISSN (electronic): 1098-2272

Publisher: Wiley-Liss Inc.

URL: https://doi.org/10.1002/gepi.22213

DOI: 10.1002/gepi.22213

PubMed id: 31298427


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