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Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics
Plasma proteomic associations with genetics and health in the UK Biobank
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Paper Summary
Conflicts of Interest
Identified Weaknesses
Rating Explanation
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Paper Summary
Paperzilla title
Your Blood Knows Your Genes (and Maybe Your Future Meds!)
This study analyzed the plasma proteome of over 54,000 UK Biobank participants, identifying thousands of genetic variations linked to blood protein levels. Many of these variations are novel and implicate genes in key biological pathways relevant to disease, potentially accelerating drug discovery and personalized medicine.
Possible Conflicts of Interest
The study was funded by a consortium of 13 biopharmaceutical companies, which raises potential conflicts of interest regarding the selection of proteins and outcomes, interpretation of results, and subsequent application of findings to drug development.
Identified Weaknesses
Limited ancestral diversity
The study acknowledges the limited representation of non-European ancestries in the UK Biobank, which hinders the generalizability of findings to diverse populations. This limits the ability to identify ancestry-specific or rare genetic associations that might be relevant for drug discovery and personalized medicine in those populations.
Limited consideration of confounders
While the study explores the impact of blood cell composition, BMI, season, and fasting time on pQTL effects, it does not extensively investigate other potential confounders such as medication use, environmental exposures, or comorbidities. These factors could influence protein levels and genetic associations, leading to spurious or biased findings.
Limited investigation of rare variants
The study focuses primarily on common genetic variants and does not comprehensively investigate the role of rare variants in regulating protein levels. Rare variants could have substantial effects on protein function and disease risk, and their exclusion limits the discovery of potential drug targets or biomarkers.
Rating Explanation
This study makes a significant contribution to the field of proteogenomics by providing a large-scale analysis of pQTLs in the UK Biobank. The identification of numerous novel genetic associations and the development of an open-access resource for the scientific community are valuable assets. However, the limited ancestral diversity, consideration of confounders, and investigation of rare variants are notable weaknesses that prevent a top rating.
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File Information
Original Title:
Plasma proteomic associations with genetics and health in the UK Biobank
File Name:
s41586-023-06592-6.pdf
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File Size:
17.57 MB
Uploaded:
July 14, 2025 at 05:07 PM
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