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Open Access Methodology article

A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis

Benjamin A Logsdon1, Gabriel E Hoffman1 and Jason G Mezey12*

Author Affiliations

1 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA

2 Department of Genetic Medicine, Weill Cornell Medical College, NY, NY, USA

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BMC Bioinformatics 2010, 11:58  doi:10.1186/1471-2105-11-58

Published: 27 January 2010

Abstract

Background

The success achieved by genome-wide association (GWA) studies in the identification of candidate loci for complex diseases has been accompanied by an inability to explain the bulk of heritability. Here, we describe the algorithm V-Bay, a variational Bayes algorithm for multiple locus GWA analysis, which is designed to identify weaker associations that may contribute to this missing heritability.

Results

V-Bay provides a novel solution to the computational scaling constraints of most multiple locus methods and can complete a simultaneous analysis of a million genetic markers in a few hours, when using a desktop. Using a range of simulated genetic and GWA experimental scenarios, we demonstrate that V-Bay is highly accurate, and reliably identifies associations that are too weak to be discovered by single-marker testing approaches. V-Bay can also outperform a multiple locus analysis method based on the lasso, which has similar scaling properties for large numbers of genetic markers. For demonstration purposes, we also use V-Bay to confirm associations with gene expression in cell lines derived from the Phase II individuals of HapMap.

Conclusions

V-Bay is a versatile, fast, and accurate multiple locus GWA analysis tool for the practitioner interested in identifying weaker associations without high false positive rates.