Consequences Of Natural Perturbations In The Human Plasma Proteome
By
Benjamin B. Sun,
Joseph C. Maranville,
James E. Peters,
David Stacey,
James R. Staley,
James Blackshaw,
Stephen Burgess,
Tao Jiang,
Ellie Paige,
Praveen Surendran,
Clare Oliver-Williams,
Mihir A. Kamat,
Bram P. Prins,
Sheri K. Wilcox,
Erik S. Zimmerman,
An Chi,
Narinder Bansal,
Sarah L. Spain,
Angela M. Wood,
Nicholas W. Morrell,
John R Bradley,
Nebojsa Janjic,
David J. Roberts,
Willem H Ouwehand,
John A. Todd,
Nicole Soranzo,
Karsten Suhre,
Dirk S. Paul,
Caroline S. Fox,
Robert M. Plenge,
John Danesh,
Heiko Runz,
Adam S. Butterworth
Posted 05 May 2017
bioRxiv DOI: 10.1101/134551
(published DOI: 10.1038/s41586-018-0175-2)
Proteins are the primary functional units of biology and the direct targets of most drugs, yet there is limited knowledge of the genetic factors determining inter-individual variation in protein levels. Here we reveal the genetic architecture of the human plasma proteome, testing 10.6 million DNA variants against levels of 2,994 proteins in 3,301 individuals. We identify 1,927 genetic associations with 1,478 proteins, a 4-fold increase on existing knowledge, including trans associations for 1,104 proteins. To understand consequences of perturbations in plasma protein levels, we introduce an approach that links naturally occurring genetic variation with biological, disease, and drug databases. We provide insights into pathogenesis by uncovering the molecular effects of disease-associated variants. We identify causal roles for protein biomarkers in disease through Mendelian randomization analysis. Our results reveal new drug targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.
Download data
- Downloaded 4,244 times
- Download rankings, all-time:
- Site-wide: 2,321
- In genomics: 264
- Year to date:
- Site-wide: 82,194
- Since beginning of last month:
- Site-wide: 82,194
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!