Why your chance of having a rare disease depends on where you live
Since the Wars of the Roses, the conflict between Lancaster and York has been woven into the fabric of Britain.
Now a study has shown the two communities are also genetically distinct, with those in isolated areas much more likely to suffer diseases, simply based on location.
Edinburgh University has found “genetic islands” of people peppered throughout the UK, where poor genetic diversity has left them susceptible to rare conditions.
Lancastrians are 73 times more likely to have Zellwegger syndrome, which disrupts cell function and can cause brain, liver and kidney problems, while Yorkshire folk are 62 times more likely to have glycogen storage disease.
The condition can cause frequent low blood sugar, muscle weakness and liver damage.
Pockets of genetic susceptibility were also found in Orkney and Shetland, where populations are at six times the risk of Bardet-Biedl syndrome. This can cause obesity, vision loss and the growth of additional fingers and toes.
Inhabitants of secluded areas in South Wales are also more likely to suffer from cystinuria, a rare condition that causes kidney stones.
The discovery has led researchers to call for tailored genetic screening to look for specific genetic variants in certain regions.
Prof Jim Flett Wilson, the study lead from the University of Edinburgh’s Usher Institute, said: “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.
“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 study examined 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.
The most genetically distinct populations were found in Shetland and Orkney, where some disease-causing variants were over 100 times more common than elsewhere in Britain.
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.
Islanders are often susceptible to rare diseases because of a lack of genetic diversity in small insular populations. But researchers also found similar problems in isolated areas of the mainland.
The team found nine disease-causing variants at much higher frequencies in Wales, and rare variants were also found to be more prevalent in areas including Lancashire, Staffordshire and Nottinghamshire.
Some cut-off areas of Staffordshire were 48 times more likely to have Retinitis pigmentosa, which can cause vision loss.
In Nottinghamshire, isolated regions were at 65 times the risk of dystrophic epidermolysis bullosa, which causes fragile skin which blisters easily.
Infants born with the disease are often referred to as “butterfly children”, because their skin is as delicate as insect wings.
Those in outlying areas of the North East are 10 times more susceptible to purine-nucleoside phosphorylase deficiency, an immune disorder which causes a shortage of white blood cells to fight off infection.
Many rare genetic conditions are only symptomatic when a person has two copies of the genetic variant. Those who have one copy may be unaware they carry the faulty gene.
The research was published in Nature Communications.