Research suggests that individuals from remote areas of the UK may possess genetic variations that heighten their risk of developing certain diseases. The study revealed that the most genetically unique populations are found in Shetland and Orkney, where some disease-causing variants – alterations in the DNA sequence that constitute a gene – are more than 100 times more prevalent compared to other regions of the UK.
Scientists also discovered that populations in north and south Wales, southeast Scotland, Ireland, and certain parts of England carry genetic variants up to 73 times more common than in the broader population. The University of Edinburgh-led research identified six disease-causing variants among those from Shetland, including one associated with Batten disease – a life-threatening neurodegenerative condition in children.
It is estimated that one in 41 Shetlanders are carriers of this condition, which can cause vision issues, seizures, poor circulation, muscle mass reduction, and spinal curvature. The disease typically manifests between the ages of five and ten and is terminal.
The team’s findings underscore the connection between ancestry and health in isolated communities, as these regions exhibit less genetic diversity compared to cities due to fewer people migrating in and out. Consequently, rare genetic variants that can trigger certain diseases can become more widespread and be inherited through generations.
Research has indicated that certain genetic variants, which can cause diseases, might only be detectable when an individual has two copies in their DNA, remaining hidden to carriers with just a single copy. This groundbreaking research scrutinised the anonymous genetic data from in excess of 44,000 individuals, sprawling across 20 territories of the UK, harnessing datasets from UK BioBank and Viking Genes studies.
However, not all parts of the UK could be represented due to data limitations. Professor Jim Wilson from the University of Edinburgh’s Usher Institute remarked: “The enrichment of otherwise rare disease-causing genetic variants in regional populations in Britain, particularly in Shetland, but also Orkney and Wales, should inform genomic medicine strategies.”
He further added: “Targeted screening for genetic disorders is common in Jewish populations, including in England. Our results show that genetic screening is also warranted in other UK communities, particularly Shetland.”
The team discovered that in Wales, nine disease-causing mutations occur at significantly elevated rates, with one variant causing a hereditary kidney stone condition being 44 times more prevalent in south Wales compared to the global populace.
The research pointed out that the 10 English regions included were not as genetically distinct.
The team suggested that the lack of geographical or cultural barriers, such as sea channels, mountains or language differences, could explain these findings. However, they discovered a number of rare variants more common in areas like Lancashire, Staffordshire and Nottinghamshire.
For instance, Lancastrians were found to be 73 times more likely than the general UK population to carry a variant linked to Zellweger syndrome, a fatal disease affecting the brain, liver and kidneys within the first year of life. The researchers emphasised the importance of further studies into rare genetic variants across the UK.
They also recommended that any future genetic screening programmes should be region-specific to include common variants. The study, funded by the Medical Research Council Human Genetics Unit, has been published in the journal Nature Communications.
