Genome sequencing has revealed insights into how current-day residents of the Faroe Islands can trace their ancestry to a North Atlantic founder population and how evolutionary forces have shaped their genomes since.
The research, previously published as a Reviewed Preprint in eLife and appearing today as the final Version of Record, uses whole-genome sequencing data from 40 Faroese individuals and is described by eLife's editors as a useful study with convincing analyses of demographic history and selection, generating results that add value beyond the region.
The Faroe Islands are situated in the North Atlantic Ocean between Iceland and Norway and are home to descendants of a founder population with a unique history shaped by population migration and periods of relative isolation. The exact settlement history of the islands is unclear, but records suggest a few founders might have arrived from Scandinavia and the British Isles around the 9th century CE, although archaeological records suggest settlement might have been earlier.
Despite the small size and remote location of the Faroe Islands, evidence from the genetic makeup of their residents suggests they may have been influenced by waves of early migration and mixing (admixture) between previously isolated northwest European and Scandinavian populations.
"No population genomic studies of this scale have yet been carried out on whole-genome sequencing data from Faroese individuals to date. An in-depth analysis of individuals' genomic architecture may reveal how the islands' demographic history has contributed to present-day health and disease in the population and may shed light on why there's a high prevalence of certain diseases such as type 2 diabetes and multiple sclerosis," explains Iman Hamid, Senior Scientist, Computational Biology, at Variant Bio, Seattle, US. Hamid is a co-first author of the study alongside Ólavur Mortensen of the Faroe Genome (FarGen) project (National Hospital of the Faroe Islands and the University of the Faroe Islands, Tórshavn, Faroe Islands) and postdoctoral researcher Alba Refoyo-Martínez (Globe Institute, University of Copenhagen).
For their study, Hamid, Mortensen, and Refoyo-Martínez set out to explore how the genetic diversity of Faroese people contributes to their health, presenting the first whole genomes of 40 individuals sequenced as part of the FarGen project. These individuals were selected to represent the genetic diversity of the broader population. Importantly, all sequencing for the study took place locally, in the FarGen laboratory on the Faroe Islands.
One genomic feature the team looked at was runs of homozygosity (ROH) – that is, continuous, unbroken stretches of homozygous (identical) genotypes along a chromosome, inherited from both parents. On average, Faroese individuals have less of their genome within short or medium-length ROHs compared to other European populations and more of the genome contained in long ROHs. Longer ROHs suggest these individuals inherited chunks of DNA from recent ancestors. This points in turn to a recent evolutionary 'bottleneck' – that is, a sharp reduction in the size of a population, leading to a significant loss of genetic diversity.
In particular, Faroese individuals have an even greater proportion of their genome contained in long ROHs than Finnish individuals, a well-known founder population and the frequent focus of studies on the health impacts of founder effects. This suggests a more recent or stronger bottleneck in the Faroese population's history and underscores the importance of investigating the health implications of these founder effects in the Faroes.
The researchers also looked for genes that underwent 'positive selection' during evolution. These are genes that provide a survival advantage or benefit and become more common in a population over time. Many of the top positively selected genes were common to both Faroese and British populations, which was unsurprising to the team given the close relationship between these groups. But there were some notable differences. For example, the lactase persistence gene, which provides the ability to digest lactose into adulthood, showed increased genetic diversity in Faroese people. This could be linked to changes in diet from the traditional reliance on animal and marine fats to later inclusion of dairy products such as milk and cheese, which were initially more limited.
Other positively selected genes unique to the population were POLQ, which is important in DNA repair and cancer, and SLC10A1, which plays a role in vitamin D absorption. This latter relationship could be significant, as the northern latitudes of the Faroe Islands and minimal UV exposure can lead to vitamin D deficiency.
One finding the team found surprising was that there was not a significant increase in the frequency of an HLA-B immune allele linked with ankylosing spondylitis, an autoimmune disease which observational evidence suggests is more prevalent in the Faroe Islands. This suggests other genetic or environmental factors might contribute to any increased risk.
Finally, in addition to identifying functional genes that were more common in Faroese people, they also explored ancestry by comparing Faroese genomes with other genome datasets of European groups spanning the last 3,000 years. These data suggest the present-day Faroese population is most likely descended from already admixed founder populations who arrived on the islands, of both Northern and Western European ancestry.
The authors and editors highlight that a finer-scale reconstruction of demographic history could yield more insights to build on these results.
"Our study highlights the impact of evolutionary processes, such as ancient admixture and positive selection, on the present-day genetic make-up of the Faroese population. Future studies should combine genomic data with physical traits to provide insights into the genetic mechanisms underlying those traits, especially those involved in autoimmune and metabolic disease on the Islands. This is the focus of the next stage of the ongoing FarGen study," concludes Noomi Gregersen, geneticist and project manager of the FarGen study, National Hospital of the Faroe Islands, and the University of the Faroe Islands. Gregersen is a co-corresponding author of the study alongside Fernando Racimo, Associate Professor at the Globe Institute, University of Copenhagen, and Stephane Castel, Co-Founder and Chief Scientific & Technology Officer at Variant Bio.
