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Image: By creating a genome-proteome map, scientists have discovered new connections between hundreds of different human diseases
.
An international research team led by scientists from the Epidemiology Group of the Medical Research Council (MRC) of the University of Cambridge, through the common origin in our genome, has discovered the connection between hundreds of different human diseases, challenging the Classification of diseases by clinical characteristics
.
A new study published in the journal Science obtained data on thousands of circulating proteins in our blood and combined these data with genetic data to create a map showing the effects of these proteins.
How genetic differences are linked together, and related diseases
Protein is the basic functional unit of the human body.
It is composed of amino acids and is encoded by our genes
.
In most medical professions and organ systems, protein failure can lead to disease, and protein is also the most common target of existing drugs
The findings published today help explain why seemingly unrelated symptoms occur in patients at the same time, and suggest that we should reconsider how the same underlying protein or mechanism can cause multiple diseases
.
When proteins become drug targets, this information can provide new strategies for the treatment of various diseases and minimize adverse reactions
In this study, the researchers used blood samples from more than 10,000 participants in the Finnish study.
The study was led by senior author Dr.
Claudia Langenberg, who worked in the Epidemiology Group of the Medical Research Council And the Berlin Institute for Health Research (Charité Universit?tsmedizin, Germany) proved that the natural variation of 2500 regions of the human genome is closely related to the difference in the abundance or function of 5000 proteins circulating in the blood
.
This approach solves an important bottleneck in transforming basic science into clinically actionable insights
.
Although large-scale studies of the human genome have found thousands of disease-related mutations in our DNA sequences, people often have potential for these mutations due to the uncertainty in the process of mapping these mutations to genes.
For example, multiple genome-wide association studies (GWAS) have linked the KAT8 region of the human genome to Alzheimer's disease, but failed to determine which gene in this region is involved in the disease
.
By combining protein and gene data, the team was able to identify a gene called PRSS8 in the KAT8 region, which encodes the protein prostaglandin, as a new candidate gene for Alzheimer's disease
The authors used these new findings to systematically test which of these protein-coding genes affect a wide range of diseases
.
They found more than 1,800 examples, of which more than one disease is driven by variations in a single gene and its protein products
Dr.
Langenberg explained: "An extreme example of a protein that we found is related to many diseases is Fibulin-3 (Fibulin-3).
We found that it is related to 37 diseases, including hyperkinesis, hernias, varicose veins, and wrists.
Low risk of tube syndrome
.
” One possible explanation is that the atypical formation of elastic fibers covering our organs and joints results in differences in elasticity between soft tissues and connective tissues
Dr.
Maik Pietzner is a researcher of the MRC Epidemiology Group and one of the main authors of the study.
He added: “Based on our genome is the key to the success of this study
.
Because we know that the detection of blood Most proteins are derived from cells in other tissues, so we integrate different biological layers, such as gene expression, allowing us to trace the protein back to disease-related tissues
In collaboration with colleagues at the Helmholtz Center in Munich, Germany, the authors developed a customized web application ( that enables immediate dissemination of research results and enables researchers from all over the world to study their most Information about genes, proteins, and diseases of interest
.
Dr.
Eleanor Wheeler is also a member of the MRC Epidemiology Team and one of the lead authors of this study.
She concluded: “For most of the genomic regions related to disease risk, the potential pathogenic genes and mechanisms are still I don’t know
.
” Our work proves the unique value of protein in amplifying disease-causing genes and helps us understand the mechanisms by which genetic variation causes disease
.
We envision that the vast amount of information we share with the scientific community will contribute to ongoing and emerging efforts to more directly link genes and diseases by encoding proteins, thereby accelerating the identification of drug targets
.
"
references:
Pietzner M.
, Wheeler E.
, et al.
Mapping the proteo-genomic convergence of human diseases.
Science 2021; 14 Oct 2021; DOI:10.
1126/science.
abj1541
DOI
10.
1126/science.
abj1541
