The landscape of hereditary haemochromatosis risk and diagnosis across the British Isles and Ireland

Highest frequency in Celtic-speaking populations has ancient origin

Hereditary haemochromatosis (HH) is one of the most common genetic conditions in people of European ancestry and leads to a build-up of iron in the body, which can poison the organs, causing liver cancer, cirrhosis and arthritis, among other things. The main cause is the major genetic risk variant, the scientific name for which is C282Y. The highest global frequencies of this variant are found in the formerly Celtic-speaking populations in Ireland and Scotland, hence haemochromatosis is sometimes called the “Celtic Curse”.

Ancient DNA showed that an Early Bronze Age individual from Rathlin, an island off the coast of Northern Ireland, was a C282Y carrier. This means the variant existed at least 4,000 years ago, and in a geographic region where it is found to be common today. 

Professor Flett Wilson said: The ancient Rathin skeleton was a carrier of haemochromatosis. This means, it has been in the Northern Ireland and Scotland area at least 4,000 years. I think that everyone in Scotland and in Ireland and England who has this variant, they all come down from a person 5,000 or 6,000 years ago and everyone is a descendant of this founder individual.

A research project, led by Professor Jim Flett Wilson of the University of Edinburgh and funded by the charity Haemochromatosis UK, has provided scientific evidence of the priority target areas where the need for population screening is highest.

The University of Edinburgh’s Viking Genes researchers and colleagues in Dublin investigated the frequency of genetic haemochromatosis within Scottish island populations, using Viking Genes data, and also data from research volunteers across the rest of Britain and Ireland.

There is considerable benefit in identifying the genetic risk for haemochromatosis, since the symptoms of the condition evolve over decades, and the opportunity to intervene and prevent disease is both simple and effective, primarily through regular blood donation. If left untreated, the progression towards iron overload can lead to a range of symptoms from changes in skin colour, chronic fatigue, joint and bone pain to liver fibrosis, cirrhosis, and cancer. The risk of haemochromatosis is higher in males than females, due at least in part to monthly blood loss in pre-menopausal women. Men with haemochromatosis are eight times more likely to develop liver cancer.

Heightened risk of haemochromatosis in people of Northwest Irish and Hebridean ancestry identifies priority areas to offer population screening

The team analysed data from >400,000 individuals to determine the genetic risk across 29 regions of the British Isles and Ireland for the major risk variant, HFE p.C282Y, and created a frequency map. 

Professor Flett Wilson said: The map will be incredibly useful. If you are trying to run a centralised healthcare system like the NHS, if you don’t know where your patient groups are it is very hard to allocate resources to the right geographic area.

Northwest Irish and Outer Hebrideans are at the highest risk (1/54 – 1/62 carry the major risk variant), higher than Northern Ireland (overall 1/71). Mainland Scots are also at increased risk (1/117), declining to 1/212 in Southern England. The Northern Isles of Scotland have low frequencies, Orkney (1/209) being similar to southern England, while Shetland (1/309) is the lowest of all the British Isles and Ireland.

The team also assessed the prevalence of a diagnosis of haemochromatosis in >63 million people in NHS England, and identified 70,365 cases. White Irish individuals have the highest prevalence (3.7x white British). Among white British, prevalence varied 11-fold from 1/1972 in parts of Kent to 1/177 in Liverpool. Discrepancies between genetic risks and prevalences for Birmingham, Cumbria, Northumberland and Durham suggest under-diagnosis in these regions. It can be speculated that the high prevalence and high genetic risk the researchers found in Merseyside may originate in part from the historically large Irish diaspora in and around Liverpool.

Analysis of grandparental origins within the Outer Hebrides shows that the C282Y variant is found at frequencies over 12% all the way from Barra and Uist in the south to Lewis in the north. We note that the estimated frequency is also very high in the Isle of Skye (15%), using the small sample available in Viking Genes. Further study is thus required to assess the degree to which Sgiathanachs (people from the Isle of Skye) would also benefit from screening.

Professor Flett Wilson added: I strongly believe there should be screening, so I saw the chance to do a study to ask where in England, Scotland, Ireland and Wales it is the most common, where are the hot-spots, are there any cold spots. Before this project it was very vague, so we have looked in 29 regions and created this map, which provides good evidence for where screening would find the most people suffering iron overload .

Torcuil Crichton, the Labour MP for Na h-Eileanan an Iar (the Western Isles), has haemochromatosis and supports Professor Flett Wilson’s call for community screening for the haemochromatosis genetic variants in the Western Isles. He has personally championed the cause in Parliament and secured a Westminster debate on 25 June 2025. Click below to read our web piece on the debate, with link to the full text of the debate on Hansard.

The 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.

This paper was published in Nature Communications. To read more visit: 

The landscape of hereditary haemochromatosis risk and diagnosis across the British Isles and Ireland 

This research was launched at Portcullis House, Westminster, on Tuesday 3rd February.

Read volunteer stories from five people who received a letter from Professor Jim Flett Wilson, telling them that they have an actionable result in the HFE gene, which can cause the iron-overload disease haemochromatosis.