Journal
NATURE GENETICS
Volume 52, Issue 10, Pages 1122-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-020-0682-6
Keywords
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Categories
Funding
- Vice-Chancellor's Fellowship from the University of Bristol
- UK Medical Research Council Integrative Epidemiology Unit [MC_UU_00011/1, MC_UU_00011/4]
- GlaxoSmithKline
- Biogen
- Cancer Research Integrative Cancer Epidemiology Programme [C18281/A19169]
- UK Medical Research Council [MR/L003120/1]
- Wellcome [102215/2/13/2]
- Turing Fellowship
- Wellcome Trust
- Royal Society [208806/Z/17/Z]
- British Heart Foundation Intermediate Clinical Research Fellowship [FS/18/23/33512]
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
- NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust
- University of Bristol
- Elizabeth Blackwell Institute for Health Research University of Bristol
- Medical Research Council
- Cancer Research UK (CRUK) [C18281/A19169]
- Bau Tsu Zung Bau Kwan Yeun Hing Research and Clinical Fellowship from the University of Hong Kong [200008682.920006.20006.400.01]
- NIHR Senior Investigator award
- CRUK Population Research Postdoctoral Fellowship [C52724/A20138]
- NIHR
- NIHR BioResource
- NIHR Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust
- NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR) [BTRU-2014-10024]
- British Heart Foundation [SP/09/002, RG/13/13/30194, RG/18/13/33946]
- MRC [MR/L003120/1, MC_PC_19009, MC_UU_00011/1, MC_UU_00002/7, MC_UU_00011/4] Funding Source: UKRI
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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 naive phenome-wide association studies of proteins. Combining MR and colocalization evidence incis-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.
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