Study maps highest hemochromatosis risk in Celtic populations

People from the Outer Hebrides and north-west Ireland have the highest risk of developing a genetic disease that causes a dangerous build-up of iron in the body, a study suggests.

The study marks the first time the genetic risk for hemochromatosis – also known as the 'Celtic curse' – has been mapped across the UK and Ireland, despite a high incidence of the condition among Scottish and Irish populations.

Targeting genetic screening for the condition to priority areas could help identify at-risk individuals earlier and avoid future health complications, experts say.

Hemochromatosis symptoms can evolve over decades as high iron levels in the body cause damage to organs. Early diagnosis and treatment – such as regular blood donation to reduce iron levels – is key to prevent liver damage, liver cancer and arthritis.

The condition is caused by small changes in DNA, known as genetic variants, which can be passed down through families. The most important risk factor in the UK and Ireland is a genetic variant called C282Y.

Scientists at the University of Edinburgh analyzed genetic data from more than 400,000 individuals in the UK BioBank and Viking Genes studies to determine the prevalence of the C282Y variant across 29 regions of the British Isles and Ireland.

They found that people with ancestry from the north-west of Ireland have the highest risk of developing haemochromatosis, with one in 54 people estimated to carry the genetic variant. This is followed by Outer Hebrideans (one in 62) and those from Northern Ireland (one in 71).

Mainland Scots – particularly in Glasgow and southwest Scotland – are also at increased risk of the condition, with one in 117 people estimated to carry the variant, corroborating the 'Celtic Curse' nickname.

The high combined genetic risk across these locations suggests that focusing genetic screening at these key areas would discover the largest number of people with the condition, researchers say.

The team also examined hemochromatosis diagnoses across NHS England and identified more than 70,000 cases. A diagnosis was nearly four times as high in white Irish individuals than in white British individuals.

Among white British individuals, those from Liverpool were 11 times more likely to have a diagnosis than those from Kent. The research team suggest this could be due to historical immigration from Ireland – more than 20 per cent of Liverpool's population was Irish in the 1850s.

The prevalence of hemochromatosis in England largely follows the pattern of genetic risk, but some regions – Birmingham, Cumbria, Northumberland and Durham – have lower rates of diagnosis than expected. These areas of potential under-diagnosis in England could also benefit from genetic screening to reveal additional cases, experts say.

Haemochromatosis prevalence data from the NHS are not available for Scotland, Wales and Northern Ireland, so could not be included.

The study, funded by the charity Haemochromatosis-UK and carried out in collaboration with RCSI University of Medicine and Health Sciences, is published in the journal Nature Communications: https://www.nature.com/articles/s41467-025-65511-7.

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."

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 prioritising 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."

Jonathan Jelley MBE JP, CEO of Haemochromatosis UK

Torcuil Crichton, the Labour MP for Na h-Eileanan an Iar (the Western Isles), has hemochromatosis and supports the call for community screening for hemochromatosis genetic variants 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 haemochromatosis 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 programme. 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."