A new study from Queen Mary University of London (QMUL) has uncovered a link between the number of ribosomal DNA (rDNA) copies in the genome and an increased risk of developing inflammatory diseases.
Ribosomal DNA, which is crucial for protein synthesis in cells, exists in hundreds of copies in the human genome. However, its repetitive nature has made it difficult to study using standard genetic analysis techniques. To combat this, researchers have now used advanced whole genome sequencing (WGS) to investigate these challenging regions—a technique analyzing the complete DNA sequence of an organism’s genome.
Published in Cell Genomics, the study analyzed data from 500,000 individuals in the UK Biobank, using specific WGS methods to count rDNA copies and correlate them with health metrics. The findings showed a strong statistical association between higher rDNA copy numbers and markers of systemic inflammation, such as the Neutrophil-to-Lymphocyte ratio (NLR), Platelet-to-Lymphocyte ratio (PLR), and Systemic Immune-Inflammation Index (SII).
These associations were observed across different ethnic groups, suggesting a universal genetic risk factor for inflammation-related diseases.
“Our research highlights the importance of analyzing the whole genome to better understand the factors impacting our health. This study demonstrates how large biobank data can lead to unexpected discoveries and open new avenues for understanding human diseases,” said Vardhman Rakyan, professor at the faculty of dentistry and medicine at QMUL and co-author of the study.
Additionally, the researchers identified a link between rDNA copy numbers and kidney function in individuals of European ancestry, with similar trends noted in other ethnicities. However, further research with larger sample sizes is needed to confirm these findings in diverse populations.
“Geneticists have long struggled to fully explain the genetic basis of many common complex traits and diseases. Our work suggests that at least part of this missing heritability resides in difficult-to-sequence regions of the genome, such as those encoding ribosomal copy number variation,” explained David Evans, professor at the University of Queensland’s Institute for Molecular Bioscience, who co-authored the study.
Victoria King, director of funding and impact at Barts Charity, who funded the study, expressed optimism about the research’s potential.
“We’re delighted to have supported this work, which could lead to better prevention and treatment for many different diseases. Using samples from UK Biobank participants, this study highlights the exciting potential of examining previously overlooked areas of the genome,” she stated.
As genetic research continues to evolve, the researchers believe that this study opens new frontiers in understanding the mechanisms of human diseases. The findings underscore the value of a comprehensive approach to genome analysis, which could lead to improved healthcare outcomes by identifying genetic risk factors previously hidden in the complexity of the genome.
