Remote UK regions linked to heightened genetic disease risk

The most genetically distinct populations were found in Shetland and Orkney, where some disease-causing variants – changes in the DNA sequence that make up a gene – were more than 100 times more common than elsewhere in the UK.

Scientists also identified populations in north and south Wales, southeast Scotland, Ireland and parts of England who carry genetic variants that are up to 73 times more common than in the general population.

The findings highlight the important link between ancestry and health, particularly among remote communities, experts say. 

Populations in isolated locations are less genetically diverse than cities, with fewer people moving into and out of the area. As a result, rare genetic variants can become common and pass down through generations.

Many rare genetic conditions are only visible when a person has two copies of the genetic variant. Those who have one copy can be unaware they carry the faulty gene.

The University of Edinburgh-led research team looked at anonymised genetic information from more than 44,000 people across 20 regions in the UK, based on data from the UK BioBank and VIKING Genes studies. They were unable to include all regions across the UK, due to a lack of data.

Six disease-causing variants were identified among those from Shetland, including one linked to Batten disease, a life-limiting neurodegenerative condition in children. An estimated one in 41 Shetlanders are carriers of the condition.

These so-called ‘genetic islands’ were found not just off the UK’s coast. The study uncovered several on the mainland.

The research team found nine disease-causing variants at much higher frequencies in Wales, including one causing an inherited form of kidney stones disorder, which is 44 times more common in south Wales than in the general population.

The ten English regions included in the study were not as genetically distinct, the study found. This could reflect the lack of geographic or cultural barriers between the regions, such as sea channels, mountains or language differences, experts say.

Despite this, a number of rare variants were found to be more prevalent in areas including Lancashire, Staffordshire and Nottinghamshire. 

People from Lancashire are 73 times more likely than the general UK population to carry a variant linked to Zellweger syndrome, a disease affecting the brain, liver and kidney, which is fatal in the first year of life.

The findings highlight the need for further research into rare genetic variants in regions across the UK. Any future genetic screening programmes, designed to identify those at risk of disease, should be tailored to include common variants in the region, the research team says.

Link

The study, funded by the MRC Human Genetics Unit, is published in the journal Nature Communications: https://www.nature.com/articles/s41467-024-51604-2