A study led by Queen Mary University of London has found 69 previously unidentified genetic determinants of rare diseases.
The research published in the journal Nature could improve rare disease diagnosis rates and pave the way for new treatments.
Rare diseases affect up to 6% of the global population. However, as many as 80% of patients remain undiagnosed after genomic sequencing due to the lack of evidence on disease-causing genetic variations.
The international team, which involved UCL researchers, developed an analytical framework to identify the causes of Mendelian diseases (genetic disorders caused by a single gene mutation) through rare variant gene burden analysis.
This was then applied to the genetic data of 34,851 patients and their family members recruited to Genomics England’s 100,000 Genomes Project.
The team discovered a total of 141 new associations, including five for which independent disease-gene evidence was recently published.
The team prioritised 69 genes that were not previously linked to rare diseases and, in 30 of these cases, the new genetic findings were supported by existing experimental evidence.
The strongest overall genetic and experimental evidence supported the newly discovered genetic variants for rare forms of diabetes,epilepsy, schizophrenia and Charcot-Marie-Tooth disease, as well as anterior segment ocular abnormalities.
Study co-author Heba Morsy, UCL Queen Square Institute of Neurology, said: “As a geneticist and bioinformatician, I find this study particularly exciting because it highlights the power of large-scale genomic analysis in uncovering previously unknown genetic causes of rare diseases.
“This research brings us one step closer to bridging the gap between genomic discovery and clinical diagnosis, ultimately helping more patients find answers and access tailored care.”
Co-author Henry Houlden, UCL Queen Square Institute of Neurology, described the study as an “excellent example of collaboration in analysing a wide spectrum of ethnically diverse patients within the UK populations”, adding that these initiatives are “essential to continue, along with continued funding for research on rare disorders, to help end the diagnostic odyssey for rare disease patients”.
