An atlas of tissue-dependent Mendelian randomization associations


Genome-wide analysis for a single trait:


Gene-centric phenome-wide association:


Gene-centric tissue-wide evaluation:


SNP-centric tissue-wide evaluation:



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Summary

This web application can be used to investigate associations between genome-wide gene expression and 395 complex traits by applying Mendelian randomization and genetic colocalization1. Analyses have been undertaken using gene expression derived from whole blood made available by the eQTLGen consortium2 (n=31,684), as well as 48 different tissue types from the GTEx project3. Findings from this web application can help uncover associations yet to be detected by genome-wide association studies and also investigate tissue-specific effects between gene expression and complex traits.

Instructions

To query results from our atlas please select parameters on the left hand side of this page before clicking the 'Search Atlas' button. This will generate results in the Tables of Results.

There are 4 ways to query the results of our atlas depending on the Input Type selected:

GWAS - Genome-wide association study. Select a complex trait and tissue of interest from the drop-down menus before clicking the 'Search Atlas' button. This will evaluate all genome-wide MR associations and plot results using a manhattan plot4.

PheWAS - Phenome-wide association study. Type in a gene and select a tissue of interest from the drop-down menus and click the 'Search Atlas' button. This will query the findings between your target gene and all traits in our atlas. An interactive plot5 will be generated to display -log10 p-values multiplied by the corresponding direction of effect for each result. As such, positive associations reside above -log10=0, whereras negative associations reside below. Points are grouped and coloured based on their corresponding traits subcategory.

Cross-tissue comparison (Gene) - Tissue-wide association study. Enter a gene and select a complex trait from the drop-down menus to investigate associations across all available tissue types. Results are plotted using an interactive plot5 as described above, except points are grouped and coloured based on tissue types.

Cross-tissue comparison (Variant) - Tissue-wide association study. Type a genetic variant (e.g. rs5882) and select a complex trait from the drop-down menus to evaluate associations across all available tissues in the atlas. If your variant is not an expression quantitative trait loci (eQTL) then a warning message will appear. As above, an interactive plot5 will be displayed with points coloured based on tissue types.

The Download button can be used to download a comma-separate value (csv) file for the results you have queried.

Citation

A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome by Tom G Richardson, Gibran Hemani, Tom R Gaunt, Caroline L Relton and George Davey Smith. bioRxiv (2019) doi: https://doi.org/10.1101/563379

About

For any queries please contact:

Tom.G.Richardson@bristol.ac.uk
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