Why is Multiple Sclerosis more common in Orkney and Shetland?

The percentage of people living with Multiple Sclerosis (MS) in Orkney and Shetland is much higher than in Scotland or the rest of the UK. A study on MS asked if particular genetic risk variants are causing this.

complex trait genetics

Common genetic risk variants are found in all human populations and each variant typically contributes a small amount to a person's risk of developing a complex disease such as MS.

In this study, risk scores were used to calculate the "genetic burden" a person carries in their genes, by assigning each individual a score dependent upon the common risk and protective variants they carry. Someone who has inherited more common risk variants will have a higher risk score and will be more likely to develop MS than someone lucky enough to inherit more protective variants.

These scores were calculated for everyone in the Orkney Complex Disease Study (ORCADES), the VIKING Healthy Study Shetland and a representative group from mainland Scotland, as part of the Generation Scotland biobank. The overall scores were then compared to determine if common risk variants are having a greater impact in the Northern Isles than mainland Scotland.

On average, the risk scores did not differ between the Northern Isles and mainland Scotland. Only one genetic variant seemed to show a significant difference between populations: HLA-DRB1. This variant is known as the most strongly-associated MS risk variant.

After investigation, HLA-DRB1 was found at a significantly higher frequency in Orkney and Shetland than mainland Scotland and is contributing a small amount to the high number of cases on the islands. Although HLA-DRB1 does have some impact on the high number of MS cases, it does not explain why the number of cases is so much higher in Orkney and Shetland.

The study also looked to see if there were any common variants for MS that were unique to the island but none were identified. However, this type of analysis relies on large numbers of patients (typically thousands); even with the high MS cases in Orkney and Shetland the total number is small, which is a limiting factor in the research.

The researchers concluded that other risk factors must be at play, either in the environment or in the genes. There may be individually rare variants influencing MS risk in some families, which are exceptionally hard to find. Research into MS risk in the islands will need to continue to confirm what other causes there may be.

If you would like to learn more, please read the publication below: