Journal article
Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
-
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(Preview, Accepted manuscript, 308.2KB, Terms of use)
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- Publisher copy:
- 10.1038/s41588-020-0682-6
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Genetics More from this journal
- Volume:
- 52
- Issue:
- 10
- Pages:
- 1122-1131
- Publication date:
- 2020-09-07
- Acceptance date:
- 2020-07-24
- DOI:
- EISSN:
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1546-1718
- ISSN:
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1546-1718
- Pmid:
-
32895551
- Language:
-
English
- Keywords:
- Pubs id:
-
1131493
- Local pid:
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pubs:1131493
- Deposit date:
-
2020-10-19
Terms of use
- Copyright holder:
- Zheng et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Author(s). Authors grant Nature Research an exclusive licence to publish, in return for which they can reuse their papers in their future printed work without first requiring permission from the publisher of the journal.
- Notes:
- This is the accepted manuscript version of the article. The final version is available from the publisher at: 10.1038/s41588-020-0682-6
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