Genetic study of proteins is a breakthrough in drug development for
complex diseases

Date:
September 7, 2020
Source:
University of Bristol
Summary:
An innovative genetic study of blood protein levels has demonstrated
how genetic data can be used to support drug target prioritization
by identifying the causal effects of proteins on diseases.



FULL STORY ==========================================================================
An innovative genetic study of blood protein levels, led by researchers
in the MRC Integrative Epidemiology Unit (MRC-IEU) at the University of Bristol, has demonstrated how genetic data can be used to support drug
target prioritisation by identifying the causal effects of proteins
on diseases.


========================================================================== Working in collaboration with pharmaceutical companies, Bristol
researchers have developed a comprehensive analysis pipeline using
genetic prediction of protein levels to prioritise drug targets, and
have quantified the potential of this approach for reducing the failure
rate of drug development.

Genetic studies of proteins are in their infancy. The aim of this
research, published in Nature Genetics, was to establish if genetic
prediction of protein target effects could predict drug trial
success. Dr Jie Zheng, Professor Tom Gaunt and colleagues from the
University of Bristol, worked with pharmaceutical companies to set up
a multi-disciplinary collaboration to address this scientific question.

Using a set of genetic epidemiology approaches, including Mendelian randomization and genetic colocalization, the researchers built a causal network of 1002 plasma proteins on 225 human diseases. In doing so, they identified 111 putatively causal effects of 65 proteins on 52 diseases, covering a wide range of disease areas.

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

"This analysis pipeline could be used to validate both efficacy and
potential adverse effects of novel drug targets, as well as provide
evidence to repurpose existing drugs to other indications.

"This study lays a solid methodological foundation for future genetic
studies of omics. The next step is for the analytical protocol to be used
in early drug target validation pipeline by the study's pharmaceutical collaborators. We hope that these findings will support further drug development?to increase the success rate of drug trials, reduce drug
cost and benefit patients," said Dr Zheng.

Tom Gaunt, Professor of Health and Biomedical Informatics, University of Bristol, and a member of the NIHR Bristol Biomedical Research Centre,
added: "Our study used publicly available data published by many
researchers around the world (collated by the MRC-IEU OpenGWAS database),
and really demonstrates the potential of open data sharing in enabling
novel discoveries in health research. We have demonstrated that this
re-use of existing data offers an efficient approach to reducing drug development costs with anticipated benefits for health and society."

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Zheng, J., Haberland, V., Baird, D. et al. Phenome-wide Mendelian
randomization mapping the influence of the plasma proteome on
complex diseases. Nat Genet, 2020 DOI: 10.1038/s41588-020-0682-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200907112327.htm

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