A landmark study has identified 69 previously unknown genetic variants linked to rare diseases, including uncommon forms of kidney disease and diabetes.
The research, involving the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, introduced a new analytical approach to identifying the genetic basis of rare diseases. The findings could improve diagnosis rates and contribute to the development of new treatments.
Rare diseases affect between four and six per cent of the global population. Despite advancements in genetic testing, the genetic cause remains unknown for many conditions, leaving approximately 80 per cent of individuals with a rare disease undiagnosed even after genomic sequencing.
To address this gap, an international team of researchers developed a method known as variant gene burden analysis. This analytical framework identifies genetic causes of Mendelian diseases, which are caused by mutations in a single gene.
The study applied this method to genetic data from 34,851 individuals and their family members, analysing a total of 72,690 genomes from Genomics England’s 100,000 Genomes Project.
Published in Nature, the study identified genetic variants in 69 genes not previously associated with any disease. In 30 of these cases, the findings were supported by existing experimental evidence, confirming the accuracy of the approach.
The strongest genetic and experimental evidence linked the newly identified variants to rare forms of kidney disease, diabetes, schizophrenia, epilepsy, Charcot-Marie-Tooth (CMT) disease, and anterior segment ocular abnormalities, which affect the development and structure of the eye.
Professor Albert Ong, Professor of Renal Medicine at the University of Sheffield and Consultant Nephrologist at Sheffield Teaching Hospitals NHS Foundation Trust, said, “Sheffield has a long and proud history of kidney disease research. This paper highlights the power of unlocking genetics through the 100,000 Genomes Project to provide hope to millions of people suffering with undiagnosed rare diseases by discovering many new genes for diseases ranging from epilepsy, diabetes, brain disorders to cystic kidney disease.”
Professor Ong, who provided expert insight on the 22 genes linked to rare kidney diseases found in the study, added, “Gene discovery is the first step towards diagnosis, a clearer understanding and the eventual development of new treatments to cure or slow disease. This is great news for patients and their families as it will provide them with an opportunity to be given a clear diagnosis. I am also proud that many patients from Sheffield contributed to this important UK project.”