Bayesian model search and multilevel inference for SNP association studies

DOI10.1214/09-AOAS322zbMATH Open1202.62166arXiv0908.1144OpenAlexW1988591324WikidataQ34416368 ScholiaQ34416368MaRDI QIDQ614148FDOQ614148

Authors: Melanie A. Wilson, Merlise A. Clyde, Scott C. Schmidler, Joellen M. Schildkraut, Edwin S. jun. Iversen 

Publication date: 27 December 2010

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Technological advances in genotyping have given rise to hypothesis-based association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among the SNPs (single nucleotide polymorphisms), choice of their genetic parametrization and missing data. In this paper we present an efficient Bayesian model search strategy that searches over the space of genetic markers and their genetic parametrization. The resulting method for Multilevel Inference of SNP Associations, MISA, allows computation of multilevel posterior probabilities and Bayes factors at the global, gene and SNP level, with the prior distribution on SNP inclusion in the model providing an intrinsic multiplicity correction. We use simulated data sets to characterize MISA's statistical power, and show that MISA has higher power to detect association than standard procedures. Using data from the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that were not identified by standard methods and have been externally ``validated in independent studies. We examine sensitivity of the NCOCS results to prior choice and method for imputing missing data. MISA is available in an R package on CRAN.

Full work available at URL: https://arxiv.org/abs/0908.1144

Recommendations

• Simultaneous SNP identification in association studies with missing data
• A Bayesian graphical model for genome-wide association studies (GWAS)
• Modeling the Association Between Clusters of SNPs and Disease Responses
• Bayesian model selection in complex linear systems, as illustrated in genetic association studies
• Bayesian Gaussian Mixture Models for High-Density Genotyping Arrays

zbMATH Keywords

lassovariable selectionBICAICBayes factorBayesian model averagingmodel uncertaintyevolutionary Monte Carlosingle nucleotide polymorphismgenetic modelsfalse discovery

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical applications (general) (92C50)

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Cited In (14)

• Bayesian Gaussian Mixture Models for High-Density Genotyping Arrays
• A new flexible Bayesian hypothesis test for multivariate data
• Joint specification of model space and parameter space prior distributions
• Bayesian model selection in complex linear systems, as illustrated in genetic association studies
• A Bayesian nonparametric multiple testing procedure for comparing several treatments against a control
• Subjective Bayesian testing using calibrated prior probabilities
• Prior distributions for objective Bayesian analysis
• Simultaneous SNP identification in association studies with missing data
• Bayesian model selection using the median probability model
• An integrated hierarchical Bayesian model for multivariate eQTL mapping
• Bayesian model search and multilevel inference for SNP association studies
• Bayesian Genome- and Epigenome-Wide Association Studies with Gene Level Dependence
• A Bayesian graphical model for genome-wide association studies (GWAS)
• A Bayesian method for detecting and characterizing allelic heterogeneity and boosting signals in genome-wide association studies

Uses Software

• R
• CRAN
• lasso2
• MISA
• LogicReg

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