Largest study on genetics of blood proteins uncovers new disease mechanisms and drug repurposing opportunities

The findings, published on 6 May in Cell, hold the potential to transform our understanding of different diseases and their treatment opportunities.

Proteins are often described as the “building blocks of life”. Our genetic code’s main purpose is to produce instructions for making proteins, which play a vital role in every part of human health, ranging from building tissues to their role in metabolism or to fight infections.

Large-scale genetic studies have been conducted for various diseases in the past two decades, with hundreds of thousands of participants involved. Although these studies revealed fundamental insights, their translation into tangible improvements for how we treat patients have been limited for various reasons, including a longstanding challenge in human genetics: identifying disease-causing genes, proteins and mechanisms underlying diseases.

Blood proteins offer a fundamental and dynamic view into human health and its many determinants. By studying the genetic regulation of blood proteins and linking this to knowledge on genetic disease causes, the authors identified new insights into how human physiology works and how such knowledge can inform drug development.

In this study, published in Cell, scientists brought together data from over 78,000 participants collected through a collaboration across 38 cohorts from different countries, the largest study of its kind.

Dr Mine Koprulu, Senior Postdoctoral Researcher in Multiomics in Queen Mary’s PHURI and a lead author of the study, said: “We are at a point where scalable measurements are possible at almost all layers of biology. This gives us an opportunity to gain a molecular view into diverse diseases, with the potential to significantly accelerate rate of discovery for new drug targets or drug repurposing opportunities”.

For example, the study reveals several lines of evidence and biomedical data to highlight that TYK2 inhibitors, which are currently used for psoriasis, can potentially be repurposed for the treatment of rheumatoid arthritis.

Professor Claudia Langenberg, senior study lead and Director of the PHURI at Queen Mary and Chair of Computational Medicine at the BIH at Charité said: “Our study is a powerful demonstration of how human molecular data can deliver new opportunities for precision medicine when generated at scale and integrated with clinical knowledge. This work would have not been possible without the dedication and collaboration of so many scientists around the world, and of course the many study participants who generously dedicated their time to research to benefit others.”

Professor Maik Pietzner, senior co-lead and Professor of Health Data Modeling at the BIH said: “There are two achievements I am particularly excited about as they open new avenues to close important gaps in research. Firstly, combining our genetic work with machine learning enabled us to better understand how human biology works, and secondly, provided evidence to help getting the right drug to the right patient.”