The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Polygenic Modeling with Bayesian Sparse Linear Mixed Models
Open accessAbstract
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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Cites
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“In referring to u as the “random effects” we are following standard terminology from LMMs. Standard terminology also refers to the coefficients ˜ β as “fixed effects”, but this phrase has a range of potential meanings [55] and so we avoid it here.”
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Cited by
Integrative approaches for large-scale transcriptome-wide association studies
Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B. W. J. H., Jansen, R., de Geus, E. J. C., Boomsma, D. I., Wright, F. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3506 · Cited by 2,479
Polygenic prediction via Bayesian regression and continuous shrinkage priors
Ge, T., Chen, C.-Y., Ni, Y., Feng, Y.-C. A., & Smoller, J. W. (2019) · Nature Communications · doi:10.1038/s41467-019-09718-5 · Cited by 1,922
Efficient Bayesian mixed-model analysis increases association power in large cohorts
Loh, P.-R., Tucker, G., Bulik-Sullivan, B. K., Vilhjálmsson, B. J., Finucane, H. K., Salem, R. M., Chasman, D. I., Ridker, P. M., Neale, B. M., Berger, B., et al. (2015) · Nature Genetics · doi:10.1038/ng.3190 · Cited by 1,507
Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores
Vilhjálmsson, B. J., Yang, J., Finucane, H. K., Gusev, A., Lindström, S., Ripke, S., Genovese, G., Loh, P.-R., Bhatia, G., Do, R., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.09.001 · Cited by 1,303
A simple new approach to variable selection in regression, with application to genetic fine mapping
Wang, G., Sarkar, A., Carbonetto, P., & Stephens, M. (2020) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/rssb.12388 · Cited by 1,121
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Metadata
- Authors
- Zhou, X., Carbonetto, P., & Stephens, M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- 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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