Understanding the Impact of Health-Related Traits in the Faroese Population
It’s been over a year since Variant Bio announced a partnership with FarGen and the University of Copenhagen. You can learn more about the project in this short film we made during one of our visits. Immediately following the announcement, the team of Faroese researchers and healthcare professionals under the direction of Dr. Noomi O. Gregersen started recruiting study participants. As I am writing this post, ~1,700 people have already participated in our joint project (called FarGen 2) and we are well on our way to our goal of recruiting 3,500 participants, approximately 6% of the population of the Faroe Islands.
Our collaboration encompasses three ambitious goals:
1. Build a Faroese genetic reference panel, which will uncover genetic variation present in the Faroese population and will become the reference for all future precision medicine efforts on the Islands;
2. Explore the genetic architecture of autoimmune and metabolic disorders on the Islands — specifically type 2 diabetes, hypertension, ankylosing spondylitis, and inflammatory bowel disease;
3. Study the evolutionary history of the Faroese people, to understand how the islands were settled, where the migrants came from, and identify evidence of natural selection in the genome.
Reaching these ambitious goals will be challenging, but at Variant Bio we have a commitment to establishing regular check-ins with participating communities and populations to ensure that they are informed about our research progress and get access to meaningful results as soon as we can provide them. With that in mind we decided to perform the first ever whole genome sequencing of samples from Faroese participants locally to support capacity building at the newly established Faroese sequencing facility, and generate preliminary results that could inform the larger study and be shared with participants. Using genealogical records and data from the first iteration of the FarGen project, a Faroese PhD student — Ólavur Mortensen — selected 40 minimally related individuals spanning the geographic regions of the Islands to be included in our pilot. Whole genome sequencing was carried out at the FarGen laboratory, and the data were analyzed jointly by FarGen, a Faroese student under the direction of Dr. Fernando Racimo at the University of Copenhagen, and population geneticists at Variant Bio.
By comparing the genomes from Faroese pilot participants to other populations around the world we find evidence that supports a close relationship between the Faroese people and people from the British Isles, which aligns with our understanding of the settlement history of the Faroe Islands. Moreover, we are able to identify genetic patterns that are unique to the Faroe Islands (and shared across all Faroese participants from the pilot). Our larger study will help us tease apart genetic relationships between these geographic regions.
We scanned the DNA from the pilot participants for signals of natural selection; that is, we looked for patterns of genetic variation that indicate certain genes may have provided a benefit (like protection against disease) for people on the Faroe Islands. We identified several signals of selection in genes whose functions are related to fundamental biological activities (immune response, sensory perception, metabolic processes, etc.), including some selection signals that are unique to the Faroese population and some that are shared with other closely-related northern European populations. With our larger study, we will have power to identify more unique selection signals and additionally leverage health and other trait information that can help us better connect these genes to the potential protective advantages they may provide.
Finally, from the genomic data, we are able to estimate the frequency of clinically-relevant genetic variants, including alleles that are known to be associated with autoimmune diseases common in the Faroese population, such as ankylosing spondylitis (AS) or inflammatory bowel disease (IBD). In the next phase of the study, we plan to leverage trait information and a larger sample size in order to investigate how these genetic findings connect to human health. It is possible that there are alternate genetic mechanisms contributing to the high prevalence of AS and IBD in the Faroes, but this is difficult to investigate with the pilot data alone.
Since this relatively small pilot project has already delivered exciting results covering Faroese population history, ancestry, and relationships between individuals, signals of positive selection, and insights into Faroese health, we decided to present these in the Faroes in a public setting. I traveled to the capital city of Tórshavn, and presented a very well received public lecture at the University of the Faroe Islands. We are looking forward to analyzing the full dataset from 3500 participants which will bring novel discoveries that can be shared with the general public. Our approach to research at Variant Bio relies on building lasting relationships, a commitment to community engagement, benefit sharing, and the return of results.
Links:
Fargen2 website and participant counter — https://www.fargen.fo/
FarGen 2 project video: https://vimeo.com/696618671
