“Celtic curse” hotspots found in Scotland and Ireland with 1 in 54 at risk

This is the first time researchers have mapped genetic risk for hemochromatosis, sometimes called the 'Celtic curse', across the UK and Ireland. The condition has long been known to affect Scottish and Irish populations at higher rates, but until now its geographic distribution had not been clearly charted.

Experts say the findings could help health officials focus genetic screening in the areas most affected, allowing people at risk to be identified earlier and treated before serious complications develop.

Iron Overload Can Damage Organs Over Decades

Hemochromatosis often develops slowly. Excess iron can accumulate in organs for years or even decades before symptoms appear. If left untreated, it can lead to liver damage, liver cancer, arthritis, and other serious health problems. Early diagnosis makes a major difference. Regular blood donation to lower iron levels is a simple and effective treatment that can prevent much of the harm.

The disease is caused by inherited changes in DNA known as genetic variants. In the UK and Ireland, the main risk factor is a variant called C282Y.

Researchers at the University of Edinburgh analyzed genetic information from more than 400,000 people who took part in the UK BioBank and Viking Genes studies. They examined how common the C282Y variant was in 29 regions across the British Isles and Ireland.

Where the C282Y Gene Variant Is Most Common

The highest rates were found among people with ancestry from north west Ireland, where about one in 54 people are estimated to carry the variant. The Outer Hebrides followed closely at one in 62, and Northern Ireland at one in 71.

Mainland Scotland also showed elevated risk, particularly in Glasgow and southwest Scotland. In those areas, about one in 117 people carry the variant, reinforcing the long standing 'Celtic Curse' nickname.

Because the combined genetic risk is so high in these regions, researchers say targeted screening there would likely identify the greatest number of people with the condition.

Diagnosis Patterns and Possible Under Detection

The team also reviewed NHS England records and found more than 70,000 diagnosed cases of hemochromatosis. White Irish individuals were nearly four times more likely to be diagnosed than white British individuals.

Among white British individuals, those living in Liverpool were 11 times more likely to have a diagnosis than people in Kent. Researchers suggest this may reflect historical Irish migration, as more than 20 percent of Liverpool's population was Irish in the 1850s.

In general, diagnosis rates in England mirror the pattern of genetic risk. However, Birmingham, Cumbria, Northumberland and Durham reported fewer cases than expected based on their genetic profiles. These areas may have undetected cases and could benefit from expanded screening efforts.

Comparable NHS prevalence data were not available for Scotland, Wales and Northern Ireland, so those regions were not included in that portion of the analysis.

The study was funded by the charity Haemochromatosis-UK and conducted in partnership with RCSI University of Medicine and Health Sciences. It was published in Nature Communications.

Calls for Community Wide Genetic Screening

Professor Jim Flett Wilson, Chair of Human Genetics at the University of Edinburgh, said: "If untreated, the iron-overload disease hemochromatosis can lead to liver cancer, arthritis and other poor outcomes. We have shown that the risk in the Hebrides and Northern Ireland is much higher than previously thought, with about one in every 60 people at risk, about half of whom will develop the disease. Early detection prevents most of the adverse consequences and a simple treatment -- giving blood -- is available. The time has come to plan for community-wide genetic screening in these high-risk areas, to identify as many people as possible whose genes mean they are at high risk of this preventable illness."

Jonathan Jelley MBE JP, CEO of Haemochromatosis UK, said: "Although there are other forms and genotypes that can lead to iron overload, available research indicates C282Y presents as the greatest risk. This hugely important work has the potential to lead to greater targeted awareness, increased diagnosis and better treatment pathways for thousands of people affected by genetic hemochromatosis.

"As a charity we have already begun work on targeting and prioritizing hotspot areas of the UK for support including with our National Helpline and clinician education. Using this study we will continue to campaign for better allocation of public resources to this preventable condition that is all too often overlooked."

Torcuil Crichton, the Labour MP for Na h-Eileanan an Iar (the Western Isles), has hemochromatosis and backs the push for screening in the Western Isles.

Torcuil Crichton MP said: "This research writes the case for community-wide screening in the Western Isles, Northern Ireland, and other hemochromatosis hotspots. I have previously raised this with Ministers in the House of Commons and this new evidence ought to be enough to persuade the UK National Screening Committee to review its position and approve a pilot screening program. The Western Isles offers a contained and distinct population sample to start from.

"Early identification, which I was lucky to have, means a whole range of bad health outcomes can be avoided and I'll be urging Ministers and the Screening Committee to reconsider their stance."