The Northern Isles Mystery: Why Orkney Has the World’s Highest Rate of Multiple Sclerosis
When you think of the remote, windswept Orkney and Shetland Islands off northern Scotland, you might imagine Viking heritage, dramatic coastlines, and resilient communities. But there’s another, more puzzling distinction that sets these islands apart: Orkney has the highest recorded prevalence of multiple sclerosis (MS) in the world — about 402 cases per 100,000 people. That’s nearly three times higher than the Scottish mainland average.
For decades, scientists have wondered: why here? Could it be the lack of sunlight and vitamin D? An isolated gene pool? Or something else entirely?
A study led by researchers at the University of Edinburgh, published in The European Journal of Human Genetics, took a deep dive into this mystery — not through environmental lenses, but through the lens of genomics. The results, however, surprised even the scientists themselves.
What They Looked At
The research team — Catriona Barnes, Caroline Hayward, David Porteous, Harry Campbell, Peter Joshi, and James Wilson — explored whether common genetic variants (those found relatively often in human populations) could explain the extraordinary rates of MS in Orkney and Shetland.
They used a powerful approach called a polygenic risk score (PRS), which essentially adds up a person’s known MS-related genetic risk variants into a single score. The higher the score, the higher the potential risk.
Data came from three major population studies:
ORCADES (Orkney Complex Disease Study) — 97 MS cases, 2,118 controls
VIKING (Shetland Health Study) — 15 MS cases, 2,090 controls
Generation Scotland — representing mainland Scots, with 30 MS cases and 8,708 controls
Altogether, they analyzed 127 genetic markers previously linked to MS.
What They Found
When they compared the DNA data, one standout genetic variant leapt off the charts — a tag SNP (rs9271069) linked to HLA-DRB1*15:01, a gene already known as the major genetic risk factor for MS worldwide.
This variant appeared in 23% of Orcadians, 21% of Shetlanders, and 17% of mainland Scots.
Statistically, this was a huge difference (p < 10⁻¹² for Orkney vs. mainland Scotland).
But here’s the twist: even this striking difference in allele frequency explained only a tiny fraction of the MS burden.
The researchers estimated that it might account for just 9 out of the 257 excess MS cases per 100,000 people in Orkney, and 6 out of 150 excess cases in Shetland.
In short, common genetic variants alone can’t explain why MS is so prevalent in the Northern Isles.
So What Might Be Going On?
The findings reinforce what’s becoming increasingly clear in MS research: this is a complex disease with both genetic and environmental roots.
Genetics: Orkney and Shetland are genetic isolates — their populations descend from small founder groups, meaning some genetic variants can become more common over time due to chance (“genetic drift”). But the study shows that this alone doesn’t account for the high MS rates.
Environment: Past studies ruled out vitamin D deficiency (Orcadians actually have higher vitamin D levels than mainland Scots) and consanguinity.
Lifestyle: Orkney also happens to have the highest obesity rate in Scotland (73% of adults), and high body mass index (BMI) is a known risk factor for MS.
Rare variants: The authors suggest that rare, yet-undiscovered genetic variants — perhaps unique to the islands — might still play a role. Whole-genome sequencing may be needed to uncover these.
What’s Next?
The team proposes a focused search for rare genetic variants that could be specific to the Northern Isles. They also call for more integrative models that blend genetics, lifestyle, and environmental exposures to get a clearer picture of what’s driving MS risk.
As Professor James Wilson notes, Orkney and Shetland remain “natural laboratories” for understanding how our genes and environment interact in shaping disease.
Takeaway
Despite decades of speculation, the genetic mystery behind Orkney’s world-leading MS rates remains unsolved. Common variants — even the notorious HLA-DRB1*15:01 — tell only part of the story. The answer likely lies in a tangle of rare genetic quirks, environmental exposures, and modern lifestyle factors unique to these remarkable islands.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Barnes, C. L. K., Hayward, C., Porteous, D. J., Campbell, H., Joshi, P. K., & Wilson, J. F. (2021). Contribution of common risk variants to multiple sclerosis in Orkney and Shetland. European Journal of Human Genetics, 29(11), 1701–1709. https://doi.org/10.1038/s41431-021-00914-w
