Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases
Tom G Richardson,
James R. Staley,
Benjamin L Elsworth,
Benjamin B. Sun,
Joseph C. Maranville,
Hannah M. Martin,
Michael V. Holmes,
Matthew R. Nelson,
George Davey Smith,
Adam S. Butterworth,
Robert A Scott,
Posted 05 May 2019
bioRxiv DOI: 10.1101/627398
Posted 05 May 2019
The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here, we estimated the effects of 1002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium (LD) is widespread in naive phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ([www.epigraphdb.org/pqtl/]). Evaluation of data from historic drug development programmes showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of our approach in identifying and prioritising potential therapeutic targets. : http://www.epigraphdb.org/pqtl/
- Downloaded 2,898 times
- Download rankings, all-time:
- Site-wide: 1,827 out of 84,692
- In genetics: 150 out of 4,445
- Year to date:
- Site-wide: 1,498 out of 84,692
- Since beginning of last month:
- Site-wide: 2,453 out of 84,692
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!