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Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions

Sarah Margaret Urbut, Gao Wang, Matthew Stephens
doi: https://doi.org/10.1101/096552
Sarah Margaret Urbut
1Department of Human Genetics/ University of Chicago, Chicago, IL USA
2Pritzker School of Medicine/Growth and Development Training Program/University of Chicago, Chicago, IL USA
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Gao Wang
1Department of Human Genetics/ University of Chicago, Chicago, IL USA
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Matthew Stephens
1Department of Human Genetics/ University of Chicago, Chicago, IL USA
3Department of Statistics/ University of Chicago, Chicago, IL USA
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Abstract

We introduce new statistical methods for analyzing genomic datasets that measure many effects in many conditions (e.g. gene expression changes under many treatments). These new methods improve on existing methods by allowing for arbitrary correlations in effects among conditions. This flexible approach increases power, improves effect-size estimates, and facilitates more quantitative assessments of effect-size heterogeneity than simple “shared/condition-specific” assessments. We illustrate these features through a detailed analysis of locally-acting (“cis”) eQTLs in 44 human tissues. Our analysis identifies more eQTLs than existing approaches, consistent with improved power. More importantly, although eQTLs are often shared broadly among tissues, our more quantitative approach highlights that effect sizes can vary considerably among tissues: some shared eQTLs show stronger effects in a subset of biologically-related tissues (e.g. brain-related tissues), or in only a single tissue (e.g. testis). Our methods are widely applicable, computationally tractable for many conditions, and available at https://github.com/stephenslab/mashr.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 09, 2017.
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Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions
Sarah Margaret Urbut, Gao Wang, Matthew Stephens
bioRxiv 096552; doi: https://doi.org/10.1101/096552
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Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions
Sarah Margaret Urbut, Gao Wang, Matthew Stephens
bioRxiv 096552; doi: https://doi.org/10.1101/096552

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