Genetic map identifies ‘Celtic Curse’ haemochromatosis hotspots across the UK and Ireland

A large population-genetics study has revealed that people with ancestry from the Outer Hebrides, Northern Ireland and north-west Ireland face the highest risk of hereditary haemochromatosis, strengthening the case for targeted genetic screening to prevent avoidable liver disease and cancer

People from the Outer Hebrides of Scotland, UK, and north-west Ireland face the highest risk of a hereditary disease that causes a dangerous accumulation of iron in the body, according to a large genetic study that has – for the first time – mapped haemochromatosis risk across the UK and Ireland.

The research has provided the most detailed regional picture to date of genetic susceptibility to haemochromatosis – also known as the ‘Celtic Curse’ – a condition that is particularly prevalent among populations of Scottish and Irish ancestry. Despite long-standing clinical recognition of this elevated risk, genetic variation associated with the disease had not previously been analysed at this geographic scale.

Researchers concluded that targeted genetic screening in high-risk regions could enable earlier diagnosis and treatment, with the potential to avert serious long-term complications. Haemochromatosis typically develops slowly over decades as excess iron damages organs, most notably the liver and joints. Without treatment, the condition can lead to cirrhosis, liver cancer and arthritis. Early diagnosis allows straightforward intervention, commonly through regular therapeutic blood donation to reduce iron levels.

Haemochromatosis arises from inherited genetic variants that disrupt the body’s ability to regulate iron absorption. In the UK and Ireland, the strongest risk factor is a variant known as C282Y. Individuals who inherit two copies of this variant are at greatest risk of iron overload, although not all carriers develop clinical disease.

Scientists at the University of Edinburgh analysed genetic data from more than 400,000 participants drawn from the UK Biobank and Viking Genes studies. The analysis examined the prevalence of the C282Y variant across 29 regions of the British Isles and Ireland, enabling fine-scale comparison of genetic risk.

The highest estimated risk was identified among people with ancestry from north-west Ireland, where approximately one in 54 individuals was found to carry the high-risk variant. This was followed by the Outer Hebrides, with one in 62 people affected, and Northern Ireland, with one in 71.

Elevated risk was also observed among mainland Scots, particularly in Glasgow and south-west Scotland, where around one in 117 individuals carried the variant. These findings lend strong genetic support to the long-used description of haemochromatosis as a ‘Celtic Curse’.

The researchers reported that the clustering of genetic risk in these regions means that geographically targeted screening would identify the greatest number of at-risk individuals for a given investment of healthcare resources.

To assess how genetic risk translated into clinical diagnosis, the team also examined haemochromatosis data from NHS England, identifying more than 70,000 recorded cases. Diagnosis rates among white Irish individuals were almost four times higher than among white British individuals. Within the white British population, people living in Liverpool were 11 times more likely to receive a diagnosis than those in Kent. The authors suggested that this pattern reflected historical migration from Ireland, noting that more than 20 per cent of Liverpool’s population was Irish during the 1850s.

Although the overall distribution of diagnoses in England broadly matched the underlying genetic risk, several regions, including Birmingham, Cumbria, Northumberland and Durham, showed lower diagnosis rates than expected. The researchers identified these areas as potential sites of under-diagnosis that could also benefit from targeted genetic screening. Comparable NHS prevalence data were not available for Scotland, Wales or Northern Ireland and could not be included in the analysis.

The study was funded by the charity Haemochromatosis UK and carried out in collaboration with Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, in Dublin, Ireland.

“If untreated, the iron-overload disease haemochromatosis can lead to liver cancer, arthritis and other poor [health] outcomes,” said Professor Jim Flett Wilson, chair of human genetics at the University of Edinburgh.

“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 – donating 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,” Flett Wilson added.

Other forms and genotypes can lead to iron overload but available research suggests that C282Y represents the greatest risk to UK and Ireland communities.

“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 haemochromatosis,” said Jonathan Jelley MBE, chief executive of Haemochromatosis UK.

“As a charity we have already begun work to target and prioritise hotspot areas of the UK for support, including through our National Helpline and clinician education.

“Using this study we will continue to campaign to secure better allocation of public resources to this preventable condition, which is too often overlooked,” he added.

Support for community screening has also come from Torcuil Crichton, Labour MP for Na h-Eileanan an Iar, who has haemochromatosis himself and has previously raised the issue in the UK Parliament.

“This research writes the case for community-wide screening in the Western Isles, Northern Ireland and other haemochromatosis hotspots,” said Crichton.

“I have raised this previously with ministers in the House of Commons and this evidence ought to persuade the UK National Screening Committee to review its position and approve a pilot screening programme.

“The Western Isles offer a contained and distinct population sample from which to start. Early identification, which I was fortunate to receive, allows avoidance of a whole range of poor health outcomes, and I will urge Ministers and the Screening Committee to reconsider their stance,” he concluded.

For further reading please visit: 10.1038/s41467-025-65511-7