Efficient Candidate Drug Target Discovery through Proteogenomics in a Scottish Cohort

Study finds links between protein levels and diseases such as type-2 diabetes and prostate cancer.

Viking Health Study—Shetland (Viking Genes) volunteer data has helped a research team at the University of Edinburgh, led by Professor Jim Flett Wilson, to understand how variants in our genes affect the levels of proteins in our blood. Proteins are the workhorses of the human body and the targets of most drugs. Understanding protein regulation is now an important element in identifying targets for new drugs or repurposing existing drugs.

Comprehensive approach helps researchers uncover the complex interactions between genes, proteins, and diseases, paving the way for new drug targets and therapies

 

What did the researchers do?

Researchers studied 6,432 different proteins in the blood of 200 people from Shetland using advanced technology. They found 505 genetic variants, called “protein quantitative trait loci”, that influence the levels of 455 proteins. Using sophisticated statistical approaches, these variants can help scientists understand the relationship between proteins and disease risk. 

Key Findings:

The study discovered new links between proteins and diseases, such as the connections between the protein ‘leukocyte receptor tyrosine kinase’ (LTK) and type-2 diabetes, and the protein ‘beta-1,3-glucuronyltransferase’ (B3GAT1) and prostate cancer.

  • 31 new genetic markers for proteins that had not been studied before
  • 43 connections between protein levels and diseases, suggesting that these proteins might play a role in causing these disorders and so potentially be worth targeting drugs to

The findings highlight the importance of studying more proteins in this way. This can help guide drug design, as drug targets with genetic support are far more likely to be successful in clinical trials. 

Professor Jim Flett Wilson said: 

Study design flowchart depicting the key analyses performed
Fig. 1 | Study design flowchart depicting the key analyses performed

This study emphasises the importance of being able to measure as many different molecules in our blood as possible. The new technology of proteomics allows us to quantify the levels of thousands of proteins, so we can better understand their regulation and relationship to disease risk, which is critical for drug development.

The paper was published in Nature Communications. To read more visit.

Efficient candidate drug target discovery through proteogenomics in a Scottish cohort 

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