Hundreds of connections between different human diseases have been uncovered through their shared origin in our genome by an international research team led by scientists from the University of Cambridge, challenging the categorization of diseases by organ, symptoms, or clinical specialty.
The study, published in Science today, generated data on thousands of proteins circulating in our blood and combined this with genetic data to produce a map showing how genetic differences that affect these proteins link together seemingly diverse as well as related diseases.
The findings help explain why seemingly unrelated symptoms can occur at the same time in patients and suggest that we should reconsider how diverse diseases can be caused by the same underlying protein or mechanism. Where a protein is a drug target, this information can point to new strategies for treating a variety of conditions, as well as minimizing adverse effects.
Using blood samples from over 10,000 participants, the team demonstrated that natural variation in 2,500 regions of the human genome is very robustly associated with differences in abundance or function of 5,000 proteins circulating in the blood.
This approach addresses an important bottleneck in the translation of basic science to clinically actionable insights. While large-scale studies of the human genome have identified many thousands of variants in our DNA sequence that are associated with disease, underlying mechanisms remain often poorly understood due to uncertainties in mapping those variants to genes. By linking such disease-related DNA variations to the abundance or function of an encoded protein, the team produced strong evidence for which genes are involved, and identified novel mechanisms by which proteins mediate genetic risk into disease onset.
The authors have also developed a web application (www.omicscience.org) to enable immediate dissemination of the results, and allow researchers worldwide to dive deeply into information on genes, proteins, and diseases they are most interested in.