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Multi-resolution localization of causal variants across the genome

View ORCID ProfileMatteo Sesia, Eugene Katsevich, Stephen Bates, Emmanuel Candès, View ORCID ProfileChiara Sabatti
doi: https://doi.org/10.1101/631390
Matteo Sesia
Stanford University, Department of Statistics, Stanford, CA 94305, USA
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Eugene Katsevich
Stanford University, Department of Statistics, Stanford, CA 94305, USA
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Stephen Bates
Stanford University, Department of Statistics, Stanford, CA 94305, USA
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Emmanuel Candès
Stanford University, Department of Statistics, Stanford, CA 94305, USA
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  • For correspondence: sabatti@stanford.edu
Chiara Sabatti
Stanford University, Department of Statistics, Stanford, CA 94305, USA
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  • ORCID record for Chiara Sabatti
  • For correspondence: sabatti@stanford.edu
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Abstract

We present KnockoffZoom, a flexible method for the genetic mapping of complex traits at multiple resolutions. KnockoffZoom localizes causal variants by testing the conditional associations of genetic segments of decreasing width while provably controlling the false discovery rate using artificial genotypes as negative controls. Our method is equally valid for quantitative and binary phenotypes, making no assumptions about their genetic architectures. Instead, we rely on well-established genetic models of linkage disequilibrium. We demonstrate that our method can detect more associations than mixed effects models and achieve fine-mapping precision, at comparable computational cost. Lastly, we apply KnockoffZoom to data from 350k subjects in the UK Biobank and report many new findings.

Footnotes

  • We have clarified the exposition in certain parts, included a discussion of the information contained in imputed variants, and added the results of further simulations and analyses in the supplement.

  • https://msesia.github.io/knockoffzoom/

Copyright 
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 November 14, 2019.
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Multi-resolution localization of causal variants across the genome
Matteo Sesia, Eugene Katsevich, Stephen Bates, Emmanuel Candès, Chiara Sabatti
bioRxiv 631390; doi: https://doi.org/10.1101/631390
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Multi-resolution localization of causal variants across the genome
Matteo Sesia, Eugene Katsevich, Stephen Bates, Emmanuel Candès, Chiara Sabatti
bioRxiv 631390; doi: https://doi.org/10.1101/631390

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