Ribosomal DNA levels increase disease risk – Institute for Molecular Biosciences

Analysis of a previously unstudied region of the human genome suggests that people with more copies of ribosomal DNA are at higher risk of developing the disease.

IMB Professor David Evans collaborated on ribosomal DNA (rDNA) research with Professor Vardman Rakian and Professor Francisco Rodríguez Algara of the Blizzard Institute, Queen Mary University of London. This is the DNA that encodes ribosomal RNA (rRNA), which is essential for making proteins in cells.

This is the world's largest genetic analysis of rDNA, which exists in hundreds of copies within the genome. This new study of 500,000 people shows that people with more copies of rDNA are more likely to develop markers of inflammation and disease throughout their lives.

Unexplored sequences of the genome

These repetitive regions of the human genome have not previously been studied using standard genetic analysis techniques. These results suggest that broader genomic analyzes may offer opportunities for preventive diagnostics, new treatments, and greater insight into the mechanisms of various human diseases.

“Geneticists have long struggled to fully explain the genetic basis of many common complex traits and diseases,” Professor Evans says.

“Our study suggests that at least some of this missing heritability resides in regions of the genome that are difficult to sequence, such as regions encoding rDNA copy number variation.”

Inflammation and kidney function

Researchers found that an individual's rDNA copy number has strong statistical associations with established systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation. I discovered that it shows gender. Immune inflammatory index (SII).

These statistically significant associations are found in the genomes of individuals of different ethnicities, suggesting common indicators of future disease risk.
rDNA copy number was also associated with individual kidney function within a sample of individuals of European descent.

Similar effects were seen in samples from other ancestry, but further studies with larger sample sizes are needed to confirm this association.

Harnessing the power of genetics

“Our study highlights the importance of analyzing the whole genome to better understand the factors that influence our health,” Professor Rakian said.

“This study is an example of how accessing large biobanks can enable unexpected discoveries and provide new avenues for harnessing the power of genetics to understand human disease.”

This research was funded by Barts Charity, Rosetrees Trust and the Biotechnology and Biological Sciences Research Council (BBSRC).

This research cell genomics.

This study includes data from the UK Biobank. This is a large biomedical database and research resource containing anonymised genetic, lifestyle and health information from 500,000 UK participants. UK Biobank's database includes blood samples, heart and brain scans and genetic data from volunteer participants, and approved researchers carrying out health-related research in the public interest from all over the world. You can access it.

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