‘Celtic curse’ genetic disease hotspots revealed in UK and Ireland

People from the Outer Hebrides and north-west Ireland have the highest risk of developing haemochromatosis – a genetic disease that causes a dangerous build-up of iron in the body – a new study suggests.

The research marks the first time the genetic risk for haemochromatosis, also known as the ‘Celtic curse’, has been mapped across the UK and Ireland, despite the high incidence of the condition among Scottish and Irish populations.

First genetic risk map for haemochromatosis

Targeting genetic screening to priority areas could help identify at-risk individuals earlier and prevent serious long-term health complications, experts say.

Haemochromatosis symptoms can evolve over decades as high iron levels damage organs. Early diagnosis and treatment – such as regular blood donation to reduce iron levels – is key to preventing liver damage, liver cancer and arthritis.

The condition is caused by small changes in DNA, known as genetic variants, which can be passed down through families. The most important risk factor in the UK and Ireland is a genetic variant called C282Y.

Scientists analysed genetic data from more than 400,000 individuals in the UK BioBank and Viking Genes studies to determine the prevalence of the C282Y variant across 29 regions of the British Isles and Ireland.

Highest risk in Ireland and the Outer Hebrides

They found that people with ancestry from the north-west of Ireland have the highest risk of developing haemochromatosis, with one in 54 people estimated to carry the genetic variant. This is followed by people from the Outer Hebrides (one in 62) and Northern Ireland (one in 71).

Mainland Scots – particularly in Glasgow and southwest Scotland – are also at increased risk, with one in 117 people estimated to carry the variant, supporting the origin of the ‘Celtic curse’ nickname.

The high combined genetic risk across these locations suggests that focusing genetic screening in these key areas would identify the largest number of people with the condition, researchers say.

NHS data reveals diagnosis gaps

The team also examined haemochromatosis diagnoses across NHS England and identified more than 70,000 cases. A diagnosis was nearly four times as high in white Irish individuals compared with white British individuals.

Among white British individuals, those from Liverpool were 11 times more likely to have a diagnosis than those from Kent. The research team suggest this could be due to historical immigration from Ireland, with more than 20 per cent of Liverpool’s population recorded as Irish in the 1850s.

While haemochromatosis prevalence in England largely follows the pattern of genetic risk, some regions – including Birmingham, Cumbria, Northumberland and Durham – show lower diagnosis rates than expected. These areas of potential under-diagnosis could also benefit from genetic screening to reveal additional cases, experts say.

Comparable NHS prevalence data are not available for Scotland, Wales and Northern Ireland and therefore could not be included.
 

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.

Jim Flett Wilson Professor of Human Genetics, Usher Institute

Although there are other forms and genotypes that can lead to iron overload, available research indicates C282Y presents as the greatest risk. 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.

As a charity we have already begun work on targeting and prioritising hotspot areas of the UK for support including with our National Helpline and clinician education. Using this study we will continue to campaign for better allocation of public resources to this preventable condition that is all too often overlooked.

Jonathan Jelley MBE JP CEO of Haemochromatosis UK
Publication date