Haemochromatosis: Mapping the ‘Celtic Curse’

As you are no doubt well aware, the spectre of haemochromatosis looms large on the Irish health landscape. Hereditary haemochromatosis is still Ireland’s most common inherited disease. In Europe, between one in 300 and one in 400 people are at risk of iron overload. In Ireland, studies have shown that our susceptibility is proportionally the highest in the world, with one in five people carrying the gene that puts them at risk.

To develop haemochromatosis, both the patient’s mother and father need to have the defective gene, and in Ireland, one in 83 people have those two genes. In Scotland, roughly one in 113 people are affected, which has helped the condition to earn the title of the ‘Celtic Curse’.

Now, some new research has pinpointed ‘hot spots’ in Ireland and Scotland where the genetic risk is highest. It’s the first time the genetic risk across Ireland and the UK has been mapped.

The work highlighted and identified some remarkable hot spots in the north-west of Ireland, as well as the Outer Hebrides, and in some areas, one in 60 people were found to have the high-risk genetic variant for haemochromatosis. In Ireland and the UK, the main risk factor is the genetic variant called C282Y.

The team from the University of Edinburgh looked at genetic data from more than 400,000 people who were part of the Viking Genes and UK Biobank studies and they examined the prevalence of C282Y across Ireland and Britain. The variant is most common among people with ancestry from the north-west of Ireland (one in 54 people), followed closely by the Outer Hebrides at one in 62, and Northern Ireland, where the genetic prevalence is one in 71.

Other areas were mapped with a lower risk than Ireland and the Outer Hebrides, but where the risk was still elevated – for example, in Glasgow and north-west Scotland approximately one in 117 people have the genetic variant.

They also looked at the broader population across the UK and found that white Irish people were almost four times more likely to be diagnosed with haemochromatosis than white British people. Those who live in Liverpool were around 11 times more likely to be diagnosed than individuals in Kent, for example, which the authors say may be linked to historical Irish migration – over 20 per cent of the population in Liverpool was Irish in the 1850s.

The study was financially supported by the charity Haemochromatosis UK, in collaboration with the RCSI University of Medicine and Health Sciences, and was published last month in Nature Communications. The authors hope their findings will prompt health officials to target their genetic screening to areas where people are at highest risk, allowing faster treatment to avoid potential complications if the condition is left untreated, such as liver cancer, arthritis, and associated liver damage, among other serious complications.

Indeed, before this research was released, in January this year it was announced that Haemochromatosis UK will offer free genetic screening to 23,500 households in Magherafelt, Ballymena, Portadown, and Irvinestown.

“The ancestors of the Ulster Scots arrived in Ulster starting over 400 years ago in the Plantation of Ulster, but continuing in subsequent decades, the majority of whom came from lowland Scotland (and some of whom are known as Scotch-Irish in the US), with others from northern England,” wrote the authors.

“In the intervening centuries, the communities have remained sufficiently structured to allow identification of the two gene pools and their different allele frequencies today. Indigenous NW [north-western] Irish have the highest overall genetic risk of haemochromatosis in the world (1/80 predicted to develop the disease by age 80 years), while Ulster Scots have half that risk (1/172), similar to that across much of mainland Scotland. We can speculate that differences may also be found between indigenous and Irish-origin communities in west-central Scotland, for example, in Larkhall and Coatbridge.”

They continued: “There are extensive Irish diasporas in the New World; for example, nearly five million Irish immigrated to the US. The increased frequencies of the p.Cys282Tyr variant and hence risk of haemochromatosis will have been carried to the New World with them, suggesting that people with significant Irish ancestry ought to be aware of a potentially heightened risk of the disease. The same is true of Hebridean descendants, for instance, in Nova Scotia, Canada…. The map of haemochromatosis risk will allow work underpinning future genetic screening programmes to be accurately targeted to the most at-risk populations first, in order to maximise the benefits by averting liver cancers, cirrhosis, arthropathy, and other negative outcomes of the disease.”

Armed with this new ‘hot-spot map’ knowledge, it would make sense, both from a patient care and health efficiency perspective, to implement geographically targeted screening for haemochromatosis with all due urgency.