Identifying genetic variants that control disease-causing blood proteins isn’t an easy task. A team led by scientists at the University of Cambridge and Merck & Co. has created a “genetic atlas” of such genetic links that could help reveal biomarkers for potential drugs to develop.
With this genetic map, the study has identified specific biological pathways—not just the genetic variants—that lead to Crohn’s disease and eczema.
“Compared to genes, proteins have been relatively understudied in human blood, even though they are the ‘effectors’ of human biology, are disrupted in many diseases, and are the targets of most medicines,” Adam Butterworth, Ph.D., of the University of Cambridge, a senior author of the study, said in a statement. “Novel technologies are now allowing us to start addressing this gap in our knowledge.”
Using SomaLogic’s SOMAscan, Butterworth and his teammates measured about 3,600 proteins in blood samples from 3,300 people and successfully identified 1,927 genetic associations with 1,478 proteins—a fourfold increase on existing knowledge, the group reported in the journal Nature.
“By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development,” wrote the researchers.
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What’s more, the atlas could also point to multiple genes that together regulate expression of a single protein. Factoring these variants into a “score” for the protein could help scientists uncover new associations between proteins and disease.
In one case, MMP12, an enzyme already tied to chronic obstructive pulmonary disease (COPD) was found to also be related to heart disease. The difference is, while higher levels of MMP12 might control the lung disease, they’re also linked to higher risk of heart disease and stroke. Translation: Drugs that target this protein to treat patients with lung disease might increase the risk of heart disease.
Aside from shedding light on potential side effects, the new genetic atlas can also guide the potential repurposing of existing drugs, or predict how molecules might perform in clinical trials, the researchers said. And all of the results from this research have been made publicly available.
“Our database is really just a starting point,” said Cambridge’s Benjamin Sun, the study’s first author, in a statement. "We’ve given some examples in this study of how it might be used, but now it’s over to the research community to begin using it and finding new applications.”