Research led by the University of Edinburgh, in collaboration with RCSI University of Medicine and Health Sciences, has mapped for the first time the genetic risk of haemochromatosis, sometimes known as the 'Celtic curse', across the UK and Ireland, identifying clear hotspots of the condition in Irish and Scottish populations.

Haemochromatosis is an inherited condition caused by small changes in DNA, known as genetic variants, that causes the body to absorb too much iron. 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 study, published in Nature Communications and funded by the charity Haemochromatosis UK, analysed genetic data from more than 400,000 people in the UK Biobank and Viking Genes studies. The research focused on a key genetic variant in the HFE gene, called C282Y, which is the most important genetic risk factor for haemochromatosis in the UK and Ireland.

The team found that people with ancestry from the north-west of Ireland have the highest estimated risk, with around one in 54 carrying the C282Y variant. This was followed by people from the Outer Hebrides, at around one in 62, and those from Northern Ireland, at around one in 71. Mainland Scots, particularly people from Glasgow and south-west Scotland, also had elevated risk, with around one in 117 estimated to carry the variant, supporting the 'Celtic curse' nickname for the condition.

To understand how this genetic risk translates into real-world disease, the researchers also examined haemochromatosis diagnoses across NHS England, identifying more than 70,000 cases. A diagnosis was nearly four times higher 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, a pattern which may reflect historical immigration from Ireland – more than 20 per cent Liverpool’s population was Irish in the 1850s.

Co-senior author Dr Edmund Gilbert, Lecturer at RCSI School of Pharmacy and Biomolecular Sciences, said: “This study really underlines that genetic haemochromatosis is part of the story of Irish health. We see particularly high genetic risk in people with ancestry from the north-west of Ireland and Northern Ireland and also in cities such as Liverpool where there has been significant historical Irish immigration. That pattern tells us that Irish communities, at home and abroad, should be a priority for awareness, genetic testing and early treatment for this condition.”

By combining regional genetic risk with mapped diagnoses of hereditary haemochromatosis, the study illustrates how health services can better plan care and pinpoint areas where the condition is likely to be underdiagnosed.

Professor Jim Flett Wilson, Chair of Human Genetics at the University of Edinburgh, said: “If untreated, the iron-overload disease haemochromatosis 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.&rdqu