The genetic landscape of MND in Scotland
Jun 2024: Researchers have analysed the DNA of hundreds of people with MND in Scotland. They have mapped the nationwide genetic landscape and compared it with that of other countries. The findings have implications for future treatment, and planning of interventions and participation in clinical trials.
In Scotland, we maintain a national register of everyone in the country with MND. This is called CARE-MND, and is led from the Anne Rowling Regenerative Neurology Clinic at the University of Edinburgh. This is an incredibly useful resource, because the vast majority of people have also consented to take part in research, which means we can look at factors causing and influencing MND across the whole country. As part of this research, many people have consented to giving a DNA sample, so that researchers can look at genetic factors that might be related to MND.
In a study that has been recently published, Dr Danielle Leighton and a team led by Prof Suvankar Pal and Prof Siddharthan Chandran analysed DNA samples generously donated by 339 people with MND. The researchers performed DNA sequencing, focusing on 48 genes that have been shown in the scientific literature to be associated with neurodegenerative diseases.
They then used the CARE-MND database to compare the genetic findings with clinical findings such as family history, age of onset, symptoms, and type of MND.
Genetics of MND in Scotland
Among the 339 people, a genetic variant known to be associated with neurodegenerative disease was identified in 44 (13%) of them. The most common genetic variant, found in 30 of the 44, was in the C9ORF72 gene. The second most common, found in 9 cases, was a variant in the SOD1 gene.
Approximately half of the people in whom a genetic variant was identified had a family history of MND.
The people carrying a variant in the C9ORF72 gene were found to have significantly lower scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), which means they had more difficulty with cognitive functions like thinking, learning and memory. As has been demonstrated before, this means that the presence of this genetic variant might lead to problems with cognition as part of MND.
Implications for people with MND
These findings provide a nationwide picture of the contribution of known genetic factors to MND in Scotland. The findings are similar but not identical to those from other countries. In particular, Scotland has a higher than average rate of SOD1 variation. Effective treatment options are now emerging for SOD1 variant carriers, which have potential to treat 4% of people with MND in Scotland.
As expected, variation in the C9ORF72 gene was the most common genetic change identified. The link between C9ORF72 variation and lower cognitive test scores means that early genetic testing of people with cognitive impairment would give them the best opportunity to plan interventions and participation in clinical drug trials.
The results were published in the Journal of Neurology. The study was funded by the Chief Scientist Office for Scotland, the MND Association, MND Scotland, and the UK Dementia Research Institute.
Related links
Read the scientific article: Genotypes and phenotypes of motor neuron disease: an update of the genetic landscape in Scotland. DOI:10.1007/s00415-024-12450-w
CARE-MND website [external]