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Identifying genes that influence the risk of disease

The risk of developing a life-changing disease is affected by both an individual’s external environment and by their genes. Many common diseases are called complex, because of the way they are influenced by multiple genes and environmental factors. Environmental influences can include (but aren’t limited to) diet, exercise and smoking. In contrast, genetic influences are passed down through our family and are written in our DNA.

Finding the genes involved in diseases like diabetes, osteoporosis, stroke, heart disease, myopia, glaucoma, chronic kidney disease and lung disease is one of the first steps on a road to developing new ways of diagnosis and treatment. These diseases greatly influence an individual’s quality of life and studying them further has the potential to help future generations significantly.

Finding the genes involved in diseases... is one of the first steps on a road to developing new ways of diagnosis and treatment.

In many communities, it can be difficult to investigate the specific part genes play, due to the variety of occupations, lifestyles and ethnic backgrounds of the population. These factors add to the complexity of pinpointing exactly how genes and gene changes affect the risk of diseases. As a result, some genetic research studies have grown in size. Examples include the 500,000 participant UK Biobank, and the All of Us Research Program, which has a recruitment target of one million Americans.

VIKING II

A different approach for getting enough data to make discoveries has been taken by Professor Jim Wilson of the University of Edinburgh. His team has launched VIKING II, the third in a series of studies focused on identifying genes that influence the risk of disease. By limiting the eligible volunteers to those with at least two grandparents from Shetland or Orkney (Scottish Islands), the environmental influences are simplified. Furthermore, the high kinship in these populations increases their usefulness for finding rare genetic variants and understanding the effects they have.

Professor Wilson has made significant research contributions across a wide range of medical disciplines. His research spans the interface of population and disease genetics, with a focus on the genetic “architecture” of complex traits and the identification of genetic variants influencing quantitative risk factors for common diseases.

ORCADES and VIKING I

The Northern Isles of Scotland (Orkney and Shetland) are isolated from the rest of the British Isles by their extreme northern geographic position. This isolation is reflected in substantial population genetic structuring, both within and between these archipelagos and mainland Britain.

In March 2011, after six years of data collection, Prof Wilson and his team finished recruitment with 2,080 participants in the Orkney Complex Disease Study (ORCADES). Each volunteer attended a clinic to give a blood sample and a cardiovascular measurement. The majority also attended further clinics as part of the ORCADES Bone and Eye Studies, where they had scans to assess bone strength and fat distribution, cognitive function testing and eye measurements.

From March 2013 – March 2015, 2,105 additional volunteers agreed to take part in a second study, VIKING Health Study – Shetland (VIKING I). This time around, each volunteer completed a postal health survey questionnaire, attended a 2-hour in-person measurement clinic and a 20-minute venepuncture clinic to give a blood and urine sample, at a dedicated research centre in Lerwick.

8 years, 2 studies and over 4000 eligible participants

ORCADES and VIKING I have together amassed more than 4,000 eligible volunteers who have contributed data and samples. These resources for health research benefit from rich clinically relevant measurements, deep genetic data and long-term follow up through health record linkage. The success of ORCADES and VIKING I is largely due to the people of Orkney and Shetland volunteering of their time, willingness to travel to clinics and coping with the somewhat invasive nature of blood sampling.

 

ORCADES and VIKING I have together amassed more than 4,000 eligible volunteers who have contributed data and samples.

 

The data collected in these studies has supported a huge range of published and ongoing research projects and collaborations. Some of these are described at www.ed.ac.uk/viking/how-you-are-helping-research. One project that particularly emphasizes the importance of the strong and enduring family links that exist in the Shetlandic population was published last year. This showcases the potential value of isolate population-based research resources for genomic medicine.

Viking II has more ambitious goals then previous studies

Following the success of these two studies, Professor Jim Wilson and his team were awarded a share of £53 million in additional funding from the Medical Research Council (MRC) to the MRC Human Genetics Unit. The new study is called VIKING II, in recognition of the Norse (Viking) ancestry of people from the Northern isles of Scotland. VIKING II was founded with ambitious goals of significantly building on the recruitment and research efforts of previous studies.

This time around, the team wanted to not only double the previous recruitment number to 8000 eligible participants, but also open up participation to the diaspora of people with at least two immediate grandparents from Orkney or Shetland living anywhere in the entire world. To accomplish this feat, the team carefully re-examined the entire recruitment and sample collection process. Any inefficiencies were weeded out and replaced with increasingly efficient methods and/or practices. Attending a research clinic can be physically difficult and require time-consuming travel. Furthermore, some potential volunteers may suffer from a phobia of needles.

Attending a research clinic can be physically difficult and require time-consuming travel. Furthermore, some potential volunteers may suffer from a phobia of needles.

Eliminating the need for blood, travel and any in-person contact

After careful thought and planning, a new workflow was put in place that eliminated the need for participant travel, the invasive collection of blood samples and any actual in-person contact with a researcher or lab. The new plan in turn allowed participants to simply and efficiently participate from the comfort of their own homes in any town, city or region in the world that had internet access and a mail service.

The new workflow came together as follows:

  • An interested individual registers online for the study
  • The volunteer gets an email with a link to a consent form and questionnaire
  • They can ask questions before giving consent and completing the questionnaire
  • The participant receives an Oragene•DNA saliva kit by mail to their home address
  • The participant provides a non-invasive saliva sample, following the simple instructions
  • The participant uses the pre-printed packet to mail the sample back
  • The lab in Edinburgh receives the sample by mail, ready for DNA extraction and analysis

Update: The effect of SARS-CoV-2

The VIKING II study was not specifically designed to continue through a worldwide pandemic! However, despite large-scale lockdowns across the globe, the VIKING II team is happy to report that because participants do the entire process from home, online and through the mail, recruitment has been able to continue when many other studies based in clinics have been forced to pause or even suspend indefinitely.

Extraordinary results speak for themselves

Following the launch in January 2020 and through the entire worldwide pandemic, VIKING II was still able to amass over 4,000 registered participants; 3,200 consented and 2,700 completed questionnaires in just 4 months. This number includes approximately 9% of people outside of the UK, including 3% from Canada. The sample return rate has been very high, with more than 2,000 samples received by the lab so far, from 2,500 kits sent out.

Oragene•DNA saliva collections kits a pivotal contributor to success

The fantastic rate of sample return (currently at 80% and rising) can largely be attributed to the ease of use of the Oragene•DNA saliva collection kits.

Participants have also been assured that the Oragene•DNA kits have a long shelf life, so they can take their time in mailing a kit back if necessary due to lockdown restrictions. As for the VIKING II research team, they are happy to know that the DNA in the saliva is very stable at normal room temperatures. This means any delay in extraction due to SARS-CoV-2 should not result in any problems with yield or quality. The lab should soon be able to resume DNA purification from the returned samples. Next steps will be to sequence the DNA and use the resulting data to extend the team’s genetics research.

As for the VIKING II research team, they are happy to know that the DNA in the saliva is very stable at normal room temperatures. This means any delay in extraction due to SARS-CoV-2 should not result in any problems with yield or quality.

Collaborations with NHS clinical geneticists in NHS Grampian have started to reveal the consequences of their unique gene pools for the people of the Northern Isles. This is because certain “actionable” variants are at much higher frequency than elsewhere – while others are lower frequency or absent. After their initial study of a rare variant in the sequence of a gene that is known to be important in the control of heart rhythm (Long QT Syndrome) in Shetland as mentioned above, the team is now moving on to a broader survey of recessive variants in Orkney and Shetland. Prof Wilson is therefore at the forefront of applying genomic medicine in Scotland, through the approved return of actionable genetic findings in the VIKING II study.

Continuing medical research

We applaud Professor Jim Wilson, the University of Edinburgh and his team for the work they have done in the past and continue to do with the VIKING II study. We are very happy our Oragene•DNA saliva kits have helped in expanding the study’s reach, excellent sample return rate and ultimately made it possible for research to continue during a time of isolation and social distancing. As the Viking II study continues, we encourage any who are interested in helping medical research to visit https://www.ed.ac.uk/viking for Viking II study details and eligibility requirements.

If you would like to try a free sample of Oragene•DNA, the same collection kits used by the VIKING II team, for your evaluation please fill out and submit the form below.

 

 

 

 

 

 

 

 

 

 

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