Inflammation and disease risk linked to ribosomal DNA copies

The number of copies of ribosomal DNA a person has, has been linked to multiple disease-associated traits.

Ribosomes are structures which are essential for protein synthesis and are found in every cell. They are coded for in an understudied portion of the genome known as ribosomal DNA (rDNA). However, rDNA is often excluded from genetic analysis since it is highly repetitive, making it difficult to analyse. Researchers at Queen Mary University in London, in collaboration with the University of Queensland, Australia used UK Biobank data to discover that rDNA copy number is associated with inflammatory markers, kidney function, and blood cell composition.

'Geneticists have long struggled to fully explain the genetic basis of many common complex traits and disease' said Professor David Evans, from the University of Queensland, who co-led the study.

'Our work suggests that at least part of this missing heritability resides in difficult-to-sequence regions of the genome, such as those encoding the variation in the number of copies of rDNA.'

The work, which was published in the journal Cell Genomics, was conducted using around half a million samples from the UK Biobank. Researchers analysed rDNA copy number and other health metrics collected on individuals. They discovered that rDNA copy number was associated with common markers of systematic inflammation.

While the initial discovery analysis was conducted using only white British individuals, the association between rDNA copies and disease-linked traits were also observed across other ancestries, suggesting that rDNA may be a common marker of disease risk.

'Our research highlights the importance of analysing the whole genome to better understand the factors impacting our health' said Professor Vardhman Rakyan, from the Blizard Institute at Queen Mary University.

He added, 'This study is also an example of how having access to large biobanks allows us to make unexpected discoveries, and provides new avenues for harnessing the power of genetics to understand human diseases.'

The ability to infer reliable information from rDNA could drive further research into the biological mechanisms which explain these findings. Additional work will also focus on verifying these results in independent cohorts and ensuring that the results apply across ancestries, authors of the study said.