Proteome-by-phenome Mendelian Randomisation detects 38 proteins with causal roles in human diseases and traits
By
Andrew Bretherick,
Oriol Canela-Xandri,
Peter Joshi,
David W Clark,
Konrad Rawlik,
Thibaud S. Boutin,
Yanni Zeng,
Carmen Amador,
Pau Navarro,
Igor Rudan,
Alan F. Wright,
Harry Campbell,
Veronique Vitart,
Caroline Hayward,
James F. Wilson,
Albert Tenesa,
Chris P Ponting,
J Kenneth Baillie,
Chris Haley
Posted 10 May 2019
bioRxiv DOI: 10.1101/631747
(published DOI: 10.1371/journal.pgen.1008785)
Target identification remains a crucial challenge in drug development. To enable unbiased detection of proteins and pathways that have a causal role in disease pathogenesis or progression, we propose proteome-by-phenome Mendelian Randomisation (P2MR). We first detected genetic variants associated with plasma concentration of 249 proteins. We then used 64 replicated variants in two-sample Mendelian Randomisation to quantify evidence of a causal role for each protein across 846 phenotypes: this yielded 509 robust protein-outcome links. P2MR provides substantial promise for drug target prioritisation. We provide confirmatory evidence for a causal role for the proteins encoded at multiple cardiovascular disease risk loci (FGF5, IL6R, LPL, LTA), and discovered that intestinal fatty acid binding protein (FABP2) contributes to disease pathogenesis. Additionally, we find and replicate evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia. Our results provide specific prediction of the effects of changes of plasma protein concentration on complex phenotypes in humans.
Download data
- Downloaded 1,168 times
- Download rankings, all-time:
- Site-wide: 15,547
- In genomics: 1,646
- Year to date:
- Site-wide: 61,570
- Since beginning of last month:
- Site-wide: 61,570
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 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!