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Polygenic Modeling with Bayesian Sparse Linear Mixed Models

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Zhou, Xiang, Carbonetto, Peter, Stephens, Matthew·2013·PLoS Genetics

Abstract

Both linear mixed models (LMMs) and sparse regression models are widely used in genetics applications, including, recently, polygenic modeling in genome-wide association studies. These two approaches make very different assumptions, so are expected to perform well in different situations. However, in practice, for a given dataset one typically does not know which assumptions will be more accurate. Motivated by this, we consider a hybrid of the two, which we refer to as a "Bayesian sparse linear mixed model" (BSLMM) that includes both these models as special cases. We address several key computational and statistical issues that arise when applying BSLMM, including appropriate prior specification for the hyper-parameters and a novel Markov chain Monte Carlo algorithm for posterior inference. We apply BSLMM and compare it with other methods for two polygenic modeling applications: estimating the proportion of variance in phenotypes explained (PVE) by available genotypes, and phenotype (or breeding value) prediction. For PVE estimation, we demonstrate that BSLMM combines the advantages of both standard LMMs and sparse regression modeling. For phenotype prediction it considerably outperforms either of the other two methods, as well as several other large-scale regression methods previously suggested for this problem. Software implementing our method is freely available from http://stephenslab.uchicago.edu/software.html.

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Metadata

Authors
Zhou, X., Carbonetto, P., & Stephens, M.
Venue
PLoS Genetics
Published
2013-02-07
Volume
9
Issue
2
Pages
e1003264
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
OpenAlex
W2962931338
Cited by
800
References
17
FWCI
27.52
Type
journal article
Language
en
Open access
gold

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Zhou, X., Carbonetto, P., & Stephens, M. (2013). Polygenic Modeling with Bayesian Sparse Linear Mixed Models. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1003264

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