September: Genetic study of proteins | News and Features

Comparison between the randomized controlled trial and the “Mendelian randomization” genetic approach.


Press release published: September 7, 2020

A groundbreaking genetic study of blood protein levels, conducted by researchers from the MRC Integrative Epidemiology Unit (MRC-IEU) at the University of Bristol, has demonstrated how genetic data can be used to support target prioritization drugs by identifying the causal effects of proteins on diseases.

Working in collaboration with pharmaceutical companies, Bristol researchers developed a comprehensive analytical pipeline using genetic prediction of protein levels to prioritize drug targets, and quantified the potential of this approach to reduce the failure rate of drug development.

Genetic studies of proteins are in their infancy. The aim of this research, published in Natural geneticswas to establish whether genetic prediction of protein target effects could predict the success of drug trials. Doctor Jie Zheng, Professor Tom Gaunt and colleagues from the University of Bristol, worked with pharmaceutical companies to set up a multidisciplinary collaboration to answer this scientific question.

Using a set of genetic epidemiology approaches, including Mendelian randomization and genetic colocalization, the researchers constructed a causal network of 1002 plasma proteins across 225 human diseases. In doing so, they identified 111 putative causal effects of 65 proteins on 52 diseases, spanning a wide range of disease domains. The results of this study are available via EpiGraphDB.

Lead author Dr. Zheng said the estimated effects of proteins on human disease could be used to predict the effects of drugs targeting these proteins.

“This analytical pipeline could be used to validate both the efficacy and potential adverse effects of new drug targets, as well as provide evidence to redirect existing drugs to other indications.

“This study establishes a solid methodological foundation for future genetic studies of omics. The next step is to use the analytical protocol in the early drug target validation pipeline by the study’s pharmaceutical collaborators. We hope these findings will support further drug development to increase the success rate of drug trials, reduce drug costs and benefit patients,” said Dr. Zheng.

Tom Gaunt, Professor of Health and Biomedical Informatics at the University of Bristol and Fellow of the NIHR Bristol Biomedical Research Center, added: “Our study used publicly available data published by many researchers around the world (collected by the MRC-IEU OpenGWAS database), and truly demonstrates the potential of open data sharing to enable new discoveries in health research. We have demonstrated that this reuse of existing data offers an efficient approach to reduce drug development costs with anticipated health and social benefits.

Paper

“Mendelian phenome-wide randomization maps the influence of the plasma proteome on complex diseases” by Jie Zheng et al inNatural genetics.

More information

This research is the result of a multidisciplinary research collaboration between the MRC’s Integrative Epidemiology Unit, Bristol Medical School, University of Bristol and pharmaceutical partners.

The CRM Integrative Epidemiology Unit at the University of Bristol (IEU) conducts some of the most advanced research in population health science in the UK. It uses genetics, demographic data and experimental interventions to search for the underlying causes of chronic diseases. The unit exploits the latest advances in genetic and epigenetic technologies. We are developing new analytical methods to improve understanding of how our family backgrounds, behaviors and genes work together. Use them to study how people grow and stay healthy or get sick.

the Data Mining Epidemiological Relationships Program, led by Professor Tom Gaunt, is funded by the UK Medical Research Council as part of the MRC Integrative Epidemiology Unit at the University of Bristol. The team is interested in understanding the mechanisms of disease, and approaches it through the integration of various biomedical and epidemiological data and the development of software tools for the analysis of these data. One of our key developments is EpiGraphDB, a database that integrates epidemiological and biomedical data to support mechanism discovery and facilitate causal inference.

About the main author

Dr. Jie Zheng is supported by the University of Bristol Vice-Chancellor’s Fellowship, which has created a unique opportunity to expand this collaboration between universities and pharmaceutical industry partners. Jie is also supported by the MRC Proximity to Discovery Industry Engagement Fund through the Elizabeth Blackwell Institute of Health Sciences at the University of Bristol to further develop causal evidence synthesis for drug development.

About the National Institute for Health Research

The National Institute for Health Research (NIHR) is the UK’s largest funder of health research and care. INRH:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social services
  • Engages and involves patients, caregivers and the public to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to meet the complex challenges of tomorrow’s health and care
  • Invests in world-class infrastructure and a skilled workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximize the value of research for patients and the economy

The NIHR was established in 2006 to improve the nation’s health and wealth through research, and is funded by the Department of Health and Human Services. In addition to its national role, the NIHR commissions have applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK support from the UK government.

About the NIHR Bristol BRC

Innovative biomedical research at the National Institute for Health Research Bristol Biomedical Research Center (NIHR Bristol BRC) takes science from the lab or computer and develops it into new drugs, treatments or health advice. Its world-renowned scientists work on many aspects of health, from the role played by individual genes and proteins to the analysis of vast collections of data on hundreds of thousands of people. Bristol BRC is unique among NIHR’s 20 BRCs across England, thanks to its expertise in groundbreaking population health research.

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