Researchers have identified genetic hotspots across the UK and Ireland for hemochromatosis, a common inherited disorder causing the body to absorb too much iron, with the highest risk concentrated in northwest Ireland and the Outer Hebrides of Scotland. The study, published in Nature Communications, marks the first comprehensive genetic mapping of the condition, often referred to as the “Celtic curse,” and could pave the way for targeted screening programs.
The research, led by the University of Edinburgh in collaboration with RCSI University of Medicine and Health Sciences, analyzed genetic data from over 400,000 participants in the UK Biobank and Viking Genes studies. Scientists focused on the C282Y variant in the HFE gene, the most significant genetic risk factor for hemochromatosis in these populations.
The findings reveal that approximately one in 54 people with ancestry from northwest Ireland carry the C282Y variant. In the Outer Hebrides, the rate is around one in 62 and in Northern Ireland, approximately one in 71. Mainland Scotland, particularly the Glasgow and southwest Scotland regions, also exhibits elevated risk, with an estimated one in 117 individuals carrying the variant.
Hemochromatosis often develops gradually, with excess iron accumulating in organs over years or even decades before symptoms manifest. Untreated, the condition can lead to severe health problems, including liver damage, liver cancer, and arthritis. Early diagnosis and treatment, such as regular blood donation to reduce iron levels, are crucial to preventing these complications.
Analysis of NHS England data revealed over 70,000 diagnosed cases of hemochromatosis. White Irish individuals were nearly four times more likely to receive a diagnosis compared to white British individuals. Significant regional variations were also observed within England, with residents of Liverpool being 11 times more likely to be diagnosed than those in Kent – a disparity researchers attribute to historical Irish migration patterns, noting that over 20 percent of Liverpool’s population had Irish roots in the 1850s.
While diagnosis rates generally mirrored genetic risk across England, researchers identified areas – Birmingham, Cumbria, Northumberland, and Durham – where diagnosed cases were lower than expected based on genetic profiles, suggesting potential underdiagnosis. Comparable data from Scotland, Wales, and Northern Ireland were not available for inclusion in this part of the analysis.
Professor Jim Flett Wilson, Chair of Human Genetics at the University of Edinburgh, emphasized the potential for preventative care. “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, CEO of Haemochromatosis UK, stated the research “has the potential to lead to greater targeted awareness, increased diagnosis and better treatment pathways for thousands of people affected by genetic hemochromatosis.” The charity has already begun prioritizing support for hotspot areas and advocating for increased public resources for the condition.
Torcuil Crichton, the Labour MP for Na h-Eileanan an Iar (the Western Isles), who himself has hemochromatosis, is urging the UK National Screening Committee to review its position and approve a pilot screening program in the Western Isles. “This research writes the case for community-wide screening in the Western Isles, Northern Ireland, and other hemochromatosis hotspots,” Crichton said. “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.”