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research article

Efficient inference for genetic association studies with multiple outcomes

Ruffieux, Hélène
•
Davison, Anthony C.  
•
Hager, Jorg
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2017
Biostatistics

Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modeling are either too simplistic to be powerful or are impracticable for computational reasons. Inspired by Richardson and others (2010, Bayesian Statistics 9), we consider a sparse multivariate regression model that allows simultaneous selection of predictors and associated responses. As Markov chain Monte Carlo (MCMC) inference on such models can be prohibitively slow when the number of genetic variants exceeds a few thousand, we propose a variational inference approach which produces posterior information very close to that of MCMC inference, at a much reduced computational cost. Extensive numerical experiments show that our approach outperforms popular variable selection methods and tailored Bayesian procedures, dealing within hours with problems involving hundreds of thousands of genetic variants and tens to hundreds of clinical or molecular outcomes.

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Type
research article
DOI
10.1093/biostatistics/kxx007
Web of Science ID

WOS:000413247300003

Author(s)
Ruffieux, Hélène
Davison, Anthony C.  
Hager, Jorg
Irincheeva, Irina
Date Issued

2017

Publisher

Oxford University Press

Published in
Biostatistics
Volume

18

Issue

4

Start page

618

End page

636

Subjects

High-dimensional data

•

Molecular quantitative trait locus analysis

•

Sparse multivariate regression

•

Statistical genetics

•

Variable selection

•

Variational inference

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
STAT  
Available on Infoscience
November 8, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/142009
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