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Biometrics. 2017 Sep;73(3):1018-1028. doi: 10.1111/biom.12649. Epub 2017 Jan 12.

Bayesian genome- and epigenome-wide association studies with gene level dependence.

Author information

1
Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota 55455, U.S.A.
2
Department of Statistical Science, Duke University, Durham, North Carolina 27708, U.S.A.

Abstract

High-throughput genetic and epigenetic data are often screened for associations with an observed phenotype. For example, one may wish to test hundreds of thousands of genetic variants, or DNA methylation sites, for an association with disease status. These genomic variables can naturally be grouped by the gene they encode, among other criteria. However, standard practice in such applications is independent screening with a universal correction for multiplicity. We propose a Bayesian approach in which the prior probability of an association for a given genomic variable depends on its gene, and the gene-specific probabilities are modeled nonparametrically. This hierarchical model allows for appropriate gene and genome-wide multiplicity adjustments, and can be incorporated into a variety of Bayesian association screening methodologies with negligible increase in computational complexity. We describe an application to screening for differences in DNA methylation between lower grade glioma and glioblastoma multiforme tumor samples from The Cancer Genome Atlas. Software is available via the package BayesianScreening for R: github.com/lockEF/BayesianScreening.

KEYWORDS:

Bayesian; DNA methylation; Genetic association study; Multiple testing; Nonparametric Bayes

PMID:
28083869
PMCID:
PMC5507757
DOI:
10.1111/biom.12649
[Indexed for MEDLINE]
Free PMC Article

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