Bayesian model comparison in genetic association analysis: linear mixed modeling and SNP set testing.

We consider the problems of hypothesis testing and model comparison under a flexible Bayesian linear regression model whose formulation is closely connected with the linear mixed effect model and the parametric models for Single Nucleotide Polymorphism (SNP) set analysis in genetic association studies. We derive a class of analytic approximate Bayes factors and illustrate their connections with a variety of frequentist test statistics, including the Wald statistic and the variance component score statistic. Taking advantage of Bayesian model averaging and hierarchical modeling, we demonstrate some distinct advantages and flexibilities in the approaches utilizing the derived Bayes factors in the context of genetic association studies. We demonstrate our proposed methods using real or simulated numerical examples in applications of single SNP association testing, multi-locus fine-mapping and SNP set association testing.

• Publication year

  2014

• Venue

  Biostatistics

• Publication date

  2014-04-29

• Fields of study

  Biology, Mathematics, Computer Science, Medicine

• Identifiers
  DOI 10.1093/biostatistics/kxv009arXiv 1404.7197PMID 25796429PMCID PMC4570575
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Advantages and pitfalls in the application of mixed-model association methods

  2014cited by this paper
• Sequence Kernel Association Test for Quantitative Traits in Family Samples

  2013influential reference
• A Unified Framework for Association Analysis with Multiple Related Phenotypes

  2013cited by this paper
• Joint analysis of functional genomic data and genome-wide association studies of 18 human traits

  2013cited by this paper
• Robust Bayesian FDR Control with Bayes Factors

  2013cited by this paper
• Bayesian model selection in complex linear systems, as illustrated in genetic association studies

  2013cited by this paper
• Polygenic Modeling with Bayesian Sparse Linear Mixed Models

  2012cited by this paper
• Dissecting the regulatory architecture of gene expression QTLs

  2012cited by this paper
• Genome-wide Efficient Mixed Model Analysis for Association Studies

  2012cited by this paper
• An efficient multi-locus mixed model approach for genome-wide association studies in structured populations

  2012cited by this paper
• A Statistical Framework for Joint eQTL Analysis in Multiple Tissues

  2012cited by this paper
• Optimal tests for rare variant effects in sequencing association studies.

  2012cited by this paper
• SNP Set Association Analysis for Familial Data

  2012cited by this paper
• BAYESIAN METHODS FOR GENETIC ASSOCIATION ANALYSIS WITH HETEROGENEOUS SUBGROUPS: FROM META-ANALYSES TO GENE-ENVIRONMENT INTERACTIONS.

  2011cited by this paper
• Rare-variant association testing for sequencing data with the sequence kernel association test.

  2011cited by this paper
• Testing for an Unusual Distribution of Rare Variants

  2011cited by this paper
• Rare-variant association testing for sequencing data with the sequence kernel association test.

  2011influential reference
• FaST linear mixed models for genome-wide association studies

  2011cited by this paper
• Bayesian variable selection regression for genome-wide association studies and other large-scale problems

  2011cited by this paper
• A Coastal Cline in Sodium Accumulation in Arabidopsis thaliana Is Driven by Natural Variation of the Sodium Transporter AtHKT1;1

  2010cited by this paper
• Variance component model to account for sample structure in genome-wide association studies

  2010cited by this paper
• Bayesian statistical methods for genetic association studies

  2009cited by this paper
• Bayes factors for genome‐wide association studies: comparison with P‐values

  2009cited by this paper
• A Groupwise Association Test for Rare Mutations Using a Weighted Sum Statistic

  2009cited by this paper
• Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data.

  2008cited by this paper
• SADDLEPOINT APPROXIMATIONS WITH APPLICATIONS.

  2007cited by this paper
• Imputation-Based Analysis of Association Studies: Candidate Regions and Quantitative Traits

  2007cited by this paper
• Calibrating a coalescent simulation of human genome sequence variation.

  2005cited by this paper
• Nonparametric Convergence Assessment for MCMC Model Selection

  2003cited by this paper
• The Bayes/Non-Bayes Compromise: A Brief Review

  1992cited by this paper
• Score Tests for Regression Models

  1983cited by this paper

• SNP fingerprint database and makers screening for current Phalaenopsis cultivars

  2025cites this paper
• Probabilistic Fine-mapping of Putative Causal Genes

  2024cites this paper
• Black Box Variational Bayes Model Averaging

  2021cites this paper
• Black Box Variational Bayesian Model Averaging

  2021cites this paper
• Bayesian averaging of computer models with domain discrepancies: a nuclear physics perspective

  2019cites this paper
• A review of kernel methods for genetic association studies

  2019cites this paper
• Ranking the importance of genetic factors by variable‐selection confidence sets

  2019cites this paper
• Inference on the Genetic Basis of Eye and Skin Color in an Admixed Population via Bayesian Linear Mixed Models

  2017cites this paper
• Molecular QTL discovery incorporating genomic annotations using Bayesian false discovery rate control

  2016cites this paper
• Ranking genetic factors related to age-related maculardegeneration by variable selection confidence sets

  2015cites this paper
• Bayesian Approximate Kernel Regression With Variable Selection

  2015cites this paper
• Scalable Bayesian Kernel Models with Variable Selection

  2015cites this paper