TY - JOUR
T1 - Genomic atlas of the human plasma proteome
AU - Sun, Benjamin B.
AU - Maranville, Joseph C.
AU - Peters, James E.
AU - Stacey, David
AU - Staley, James R.
AU - Blackshaw, James
AU - Burgess, Stephen
AU - Jiang, Tao
AU - Paige, Ellie
AU - Surendran, Praveen
AU - Oliver-Williams, Clare
AU - Kamat, Mihir A.
AU - Prins, Bram P.
AU - Wilcox, Sheri K.
AU - Zimmerman, Erik S.
AU - Chi, An
AU - Bansal, Narinder
AU - Spain, Sarah L.
AU - Wood, Angela M.
AU - Morrell, Nicholas W.
AU - Bradley, John R.
AU - Janjic, Nebojsa
AU - Roberts, David J.
AU - Ouwehand, Willem H.
AU - Todd, John A.
AU - Soranzo, Nicole
AU - Suhre, Karsten
AU - Paul, Dirk S.
AU - Fox, Caroline S.
AU - Plenge, Robert M.
AU - Danesh, John
AU - Runz, Heiko
AU - Butterworth, Adam S.
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Ltd., part of Springer Nature.
PY - 2018/6/7
Y1 - 2018/6/7
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85048231672
U2 - 10.1038/s41586-018-0175-2
DO - 10.1038/s41586-018-0175-2
M3 - Article
C2 - 29875488
AN - SCOPUS:85048231672
SN - 0028-0836
VL - 558
SP - 73
EP - 79
JO - Nature
JF - Nature
IS - 7708
ER -
