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Article
License: CC BY ND
Data sources: UnpayWall
https://doi.org/10.1101/236869...
Article . 2017 . Peer-reviewed
Data sources: Crossref
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Probabilistic fine-mapping of transcriptome-wide association studies

Authors: Mancuso, Nicholas; Kichaev, Gleb; Shi, Huwenbo; Freund, Malika; Gusev, Alexander; Pasaniuc, Bogdan;

Probabilistic fine-mapping of transcriptome-wide association studies

Abstract

Abstract Transcriptome-wide association studies (TWAS) using predicted expression have identified thousands of genes whose locally-regulated expression is associated to complex traits and diseases. In this work, we show that linkage disequilibrium (LD) among SNPs induce significant gene-trait associations at non-causal genes as a function of the overlap between eQTL weights used in expression prediction. We introduce a probabilistic framework that models the induced correlation among TWAS signals to assign a probability for every gene in the risk region to explain the observed association signal while controlling for pleiotropic SNP effects and unmeasured causal expression. Importantly, our approach remains accurate when expression data for causal genes are not available in the causal tissue by leveraging expression prediction from other tissues. Our approach yields credible-sets of genes containing the causal gene at a nominal confidence level (e.g., 90%) that can be used to prioritize and select genes for functional assays. We illustrate our approach using an integrative analysis of lipids traits where our approach prioritizes genes with strong evidence for causality.

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Average
Average
Top 10%
Green