RT Journal Article
SR Electronic
T1 Consequences of natural perturbations in the human plasma proteome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 134551
DO 10.1101/134551
A1 Benjamin B. Sun
A1 Joseph C. Maranville
A1 James E. Peters
A1 David Stacey
A1 James R. Staley
A1 James Blackshaw
A1 Stephen Burgess
A1 Tao Jiang
A1 Ellie Paige
A1 Praveen Surendran
A1 Clare Oliver-Williams
A1 Mihir A. Kamat
A1 Bram P. Prins
A1 Sheri K. Wilcox
A1 Erik S. Zimmerman
A1 An Chi
A1 Narinder Bansal
A1 Sarah L. Spain
A1 Angela M. Wood
A1 Nicholas W. Morrell
A1 John R. Bradley
A1 Nebojsa Janjic
A1 David J. Roberts
A1 Willem H. Ouwehand
A1 John A. Todd
A1 Nicole Soranzo
A1 Karsten Suhre
A1 Dirk S. Paul
A1 Caroline S. Fox
A1 Robert M. Plenge
A1 John Danesh
A1 Heiko Runz
A1 Adam S. Butterworth
YR 2017
UL http://biorxiv.org/content/early/2017/05/05/134551.abstract
AB 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.