Inside the push to screen Scottish islanders for rare disease-causing 'mutated' variants

Jim Wilson, professor of human genetics at the University of Edinburgh’s Usher Institute, said greater resources and political will were required to establish island-wide genomic screening projects. He said this would allow people to understand if they are carrying actionable or recessive variants that could lead to the likes of breast cancer and cardiomyopathies.

Prof Wilson said the roll-out of such genetic tests would ultimately save the NHS in Scotland money in the long run, given it would allow for interventionary measures to take place before people become unwell. He stressed that inaugurating a pilot screening project in Shetland would demonstrate its efficacy.

Earlier this year, a team led by Prof Wilson unveiled research into the genetic variants in populations living in the northern isles. The study, published in the Nature Communications journal, identified six disease-causing variants that were especially enriched in Scotland’s most northerly archipelago. Around one in 40 Shetlanders was shown to be carrying a genetic variant linked to Batten disease, a fatal neurodegenerative condition that typically begins in childhood.

Prof Wilson pointed to other genetic programmes designed to establish health risks in subsets of the population, such as an NHS England drive to screen tens of thousands of people of Jewish ancestry, some of whom, like many Shetlanders, are carrying BRCA gene mutations that increase their chances of developing cancer.

“We found numerous founder effects in Shetland, some of them really disturbing,” Prof Wilson explained. “Batten disease is a rare disorder where a baby is born completely normal, but there’s essentially a neurodegeneration, and it’s fatal - the child dies before his or her teenage years are finished. It’s a really horrific disease, and one in 40 Shetlanders is a carrier. There’s a non-trivial chance that Shetlanders could get together and bring more Batten babies into the world.

“Initially I thought people in Shetland should be screened for BRCA2 [a variant that can impart very high risks of breast and ovarian cancer for women, as well male breast cancer and prostate cancer]. But now I’m starting to believe that they ought to be screened for a panel of different variants, both actionable variants and those that will influence their children’s health.

“It’s an effort to get people into screening. You’ve got to raise awareness in the community and raise funds. You might as well have a one-stop shop and do it all in a one-er.”

In an interview with The Genetics Podcast, Prof Wilson said he believed that routine genetic screening would become a “normal part” of everyday healthcare within the next half century. But he emphasised there was no good reason not to introduce it sooner.

He is focused on making the case for island-wide screening initiatives in the first instance, but said the detection of mutated genes ought also to extend to the wider diaspora of those of Shetlandic and Orcadian heritage now living elsewhere in Scotland or further afield.

“I’m trying now to publish a good evidence base for what this screening would be like. At the moment, there’s no screening like this available to these islanders, and it’s actually an inequitable situation, because the Jewish community, just as of last year, have a scheme called J-BRCA, whereby anyone with one or more Jewish grandparents who is cared for by NHS England can have a BRCA test.

“We need the exact same thing for the islands of Scotland, and indeed, the Jewish community in Scotland, who can’t at the moment take advantage of this. It’s given me good arguments to have with politicians and the NHS, because J-BRCA is up and running, and I’m a great supporter of it. But we need something like that for people in the Scottish islands, and indeed, for their descendants who’ve moved to Edinburgh, Glasgow and all over.”

He added: “What’s important is that the cost of this is a drop in the ocean compared to the expenditure across the whole NHS, or even the Scottish NHS, and the gains are not only avoiding Batten babies. We’ve identified at least eight other conditions that we’d hope to avoid.”

Prof Wilson’s work on genetic epidemiology studies is informed by his own heritage, given he is descended on his father’s side from the Wilsons of Fair Isle, who go back 12 generations on the remote island, situated midway between Shetland and Orkney. To this day, most families there can trace a shared ancestor who was born in 1775.

Prof Wilson has already met with officials in Shetland and Holyrood about his work in an attempt to raise awareness and change policy around broader genetic screening programmes, which are well-established in the likes of Finland and the US. He admitted the roll-out of such a scheme Scotland-wide would have considerable resource implications, but stressed that finances were not the only constraints he had encountered.

“I think there’s an old-fashioned view in clinical genetics that’s very much focused on not worrying people,” he reasoned. “People will say to me ‘but Jim, you’re sentencing these people to a lifetime of worry’. And I’m like ‘but they need to know’.

“If I was a carrier of a haemochromatosis pathogenic variant, I would want to know. It means that I would have an eight-fold chance of liver cancer. These are really important things.”