Genomic atlas of the human plasma proteome

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 and Adam S. Butterworth ()
Additional contact information
Benjamin B. Sun: University of Cambridge
Joseph C. Maranville: MRL, Merck & Co., Inc.
James E. Peters: University of Cambridge
David Stacey: University of Cambridge
James R. Staley: University of Cambridge
James Blackshaw: University of Cambridge
Stephen Burgess: University of Cambridge
Tao Jiang: University of Cambridge
Ellie Paige: University of Cambridge
Praveen Surendran: University of Cambridge
Clare Oliver-Williams: University of Cambridge
Mihir A. Kamat: University of Cambridge
Bram P. Prins: University of Cambridge
Sheri K. Wilcox: SomaLogic Inc
Erik S. Zimmerman: SomaLogic Inc
An Chi: MRL, Merck & Co., Inc.
Narinder Bansal: University of Cambridge
Sarah L. Spain: Wellcome Trust Genome Campus, Hinxton
Angela M. Wood: University of Cambridge
Nicholas W. Morrell: Addenbrooke’s Hospital
John R. Bradley: Cambridge University Hospitals
Nebojsa Janjic: SomaLogic Inc
David J. Roberts: University of Oxford, John Radcliffe Hospital
Willem H. Ouwehand: Addenbrooke’s Hospital
John A. Todd: University of Oxford
Nicole Soranzo: Addenbrooke’s Hospital
Karsten Suhre: Weill Cornell Medicine–Qatar
Dirk S. Paul: University of Cambridge
Caroline S. Fox: MRL, Merck & Co., Inc.
Robert M. Plenge: MRL, Merck & Co., Inc.
John Danesh: University of Cambridge
Heiko Runz: MRL, Merck & Co., Inc.
Adam S. Butterworth: University of Cambridge

Nature, 2018, vol. 558, issue 7708, 73-79

Abstract: Abstract Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (31)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0175-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:558:y:2018:i:7708:d:10.1038_s41586-018-0175-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0175-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().