“Celtic Curse” Hotspots Identified: Genetic Risk of Iron Overload Mapped Across the UK and Ireland

People with ancestry from the Outer Hebrides and north-west Ireland face a significantly elevated risk of developing hemochromatosis, a genetic disorder causing excessive iron absorption. Researchers have, for the first time, mapped the genetic risk of this condition – often called the “Celtic curse” – across the UK and Ireland, revealing striking regional hotspots.

Understanding Hemochromatosis: The ‘Celtic Curse’

Hemochromatosis is a hereditary disease characterized by the buildup of dangerous levels of iron in the body. This excess iron can accumulate in organs like the liver, heart, and joints over years or even decades, potentially leading to severe health problems if left untreated. These include liver damage, liver cancer, and arthritis.

The condition is most commonly caused by variants in the HFE gene, particularly the C282Y variant, and is more prevalent in individuals of Irish and Scottish descent.

New Genetic Mapping Reveals Risk Hotspots

A recent study, published in Nature Communications, analyzed genetic information from over 400,000 participants in the UK BioBank and Viking Genes studies. Researchers examined the prevalence of the C282Y gene variant across 29 regions of the British Isles, and Ireland.

The findings revealed:

• North-west Ireland: Approximately one in 54 people carry the high-risk C282Y gene variant.
• Outer Hebrides: Roughly one in 62 people carry the variant.
• Northern Ireland: About one in 71 people carry the variant.
• Mainland Scotland: Elevated risk was observed, particularly in Glasgow and southwest Scotland, where approximately one in 117 people carry the variant.

Diagnosis and Potential Underdetection

Analysis of NHS England records showed 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.

Within white British individuals, those residing in Liverpool were 11 times more likely to be diagnosed than those in Kent. Researchers attribute this to historical Irish migration patterns, noting that over 20% of Liverpool’s population had Irish roots in the 1850s.

Areas like Birmingham, Cumbria, Northumberland, and Durham reported fewer cases than expected based on their genetic profiles, suggesting potential underdiagnosis and a need for expanded screening. Comparable data from Scotland, Wales, and Northern Ireland were not available for this portion of the analysis.

Calls for Targeted Screening

Experts are advocating for community-wide genetic screening in high-risk areas to identify individuals who may be at risk. Early detection is crucial, as treatment is simple and effective. Regular blood donation can lower iron levels and prevent serious complications.

“If untreated, the iron-overload disease hemochromatosis can lead to liver cancer, arthritis and other poor 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 — 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 MBE JP, CEO of Haemochromatosis UK, emphasized the importance of this research for increasing awareness, diagnosis, and treatment pathways.

Torcuil Crichton, the Labour MP for Na h-Eileanan an Iar (the Western Isles), who himself has hemochromatosis, supports the push for screening in the Western Isles and is urging the UK National Screening Committee to review its position and approve a pilot screening program.