Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex disease...
Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases
About this item
Full title
Author / Creator
Zheng, Jie , Haberland, Valeriia , Baird, Denis , Walker, Venexia , Haycock, Philip C. , Hurle, Mark R. , Gutteridge, Alex , Erola, Pau , Liu, Yi , Luo, Shan , Robinson, Jamie , Richardson, Tom G. , Staley, James R. , Elsworth, Benjamin , Burgess, Stephen , Sun, Benjamin B. , Danesh, John , Runz, Heiko , Maranville, Joseph C. , Martin, Hannah M. , Yarmolinsky, James , Laurin, Charles , Holmes, Michael V. , Liu, Jimmy Z. , Estrada, Karol , Santos, Rita , McCarthy, Linda , Waterworth, Dawn , Nelson, Matthew R. , Smith, George Davey , Butterworth, Adam S. , Hemani, Gibran , Scott, Robert A. and Gaunt, Tom R.
Publisher
New York: Nature Publishing Group US
Journal title
Language
English
Formats
Publication information
Publisher
New York: Nature Publishing Group US
Subjects
More information
Scope and Contents
Contents
The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in
cis
-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes (
https://www.epigraphdb.org/pqtl/
). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.
Mendelian randomization (MR) and colocalization analyses are used to est...
Alternative Titles
Full title
Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases
Authors, Artists and Contributors
Author / Creator
Haberland, Valeriia
Baird, Denis
Walker, Venexia
Haycock, Philip C.
Hurle, Mark R.
Gutteridge, Alex
Erola, Pau
Liu, Yi
Luo, Shan
Robinson, Jamie
Richardson, Tom G.
Staley, James R.
Elsworth, Benjamin
Burgess, Stephen
Sun, Benjamin B.
Danesh, John
Runz, Heiko
Maranville, Joseph C.
Martin, Hannah M.
Yarmolinsky, James
Laurin, Charles
Holmes, Michael V.
Liu, Jimmy Z.
Estrada, Karol
Santos, Rita
McCarthy, Linda
Waterworth, Dawn
Nelson, Matthew R.
Smith, George Davey
Butterworth, Adam S.
Hemani, Gibran
Scott, Robert A.
Gaunt, Tom R.
Identifiers
Primary Identifiers
Record Identifier
TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7610464
Permalink
https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7610464
Other Identifiers
ISSN
1061-4036
E-ISSN
1546-1718
DOI
10.1038/s41588-020-0682-6
