Study sheds light on variation in genes that affect drug response in Scottish Islanders, paving the way for precision medicine. A small team of researchers from Scotland and South Africa studied the distribution of genetic differences in people from the Shetland and Orkney Isles and predicted how they might affect their response to medications, based on published guidelines. This is part of a growing field called pharmacogenomics, which looks at how our genes influence the way drugs work in our bodies. The study used genetic data from over 1,800 people who took part in the Viking Genes programme, a research initiative focused on the unique genetics of people living in these northern Scottish islands. Scientists looked at 41 genes known to play a role in how drugs are absorbed, processed, and used by the body.They found that everyone in the study had at least one known genetic variant that could affect how they respond to certain medications. For some drugs, up to half of the participants had genetic findings that indicate they might require a change in the dose or type of medication. The most commonly affected drug-related genes were those involved in processing common medications like antidepressants, painkillers, blood thinners, and statins.While most genetic patterns were similar to those found in other European populations, the study also found rare and potentially new genetic variants that were more common in Shetland and Orkney, albeit with uncertain functional implications. Some of these rare variants were traced back to ancestors who lived hundreds of years ago, showing how isolated communities can develop unique genetic characteristics. Chart illustrating predicted pharmacogene phenotype variability (left) across Orcadian and Shetlander study populations in Viking Genes and the proportion of participants that may benefit from genomics-informed drug therapy (right). Precision MedicineThe researchers suggest that, starting with variants with known impacts on drug response, genetic testing before prescribing medication could be beneficial for people in Shetland and Orkney. This approach, known as precision medicine, could lead to safer and more effective treatments.Understanding genetic differences in patients, alongside other determinants (e.g. age, sex, lifestyle, microbiome, and prior/existing treatments), can help doctors:Choose the right medication and dose for each personMitigate side effectsImprove treatment outcomesProfessors Jim Flett Wilson and Tim Aitman (University of Edinburgh), and Dr David Twesigomwe (University of the Witwatersrand, South Africa), analysed the Orkney and Shetland data, looking at variants in genes which influence the metabolism/transport/effect of drugs, their efficacy (how well they work in a given person) and the likelihood of adverse reactions. Professor Flett Wilson said: In the future, people will know a lot about their DNA, including details of the variants that influence how their body deals with medications. This means that when they need a prescription, the pharmacist will know which dose to start them on, rather than using trial-and-error, as is the case today. They’ll also know which drugs to avoid in that person, as they wouldn’t work or would provoke a bad reaction. We aren’t quite there yet for many reasons, but this paper provides some groundwork for what this would look like in the Scottish Isles.Dr Twesigomwe said:Pharmacogenomics can enable healthcare teams to obtain an important piece of the puzzle to make the optimal choice of drug/dose for each patient, the first time. For example, we observed that 7.8% of the Shetlander participants and 8.6% of the Orcadian participants in the study had no functional copies of the important CYP2D6 gene. These participants are predicted to be CYP2D6 poor metabolisers and may therefore not respond adequately to some pain medications such as codeine and tramadol, while they could be at a risk of side effects to some antidepressants (e.g. paroxetine). For context, the proper functioning of CYP2D6 is vital to the response of about 20% of commonly prescribed medications. Broadly, this paper highlights the extent of known and novel variation across important genes present in state-of-the-art pharmacogenomic tests. This research can inform the application of pharmacogenomic tests and future studies on their clinical utility with regard to improving drug therapeutic outcomes across the Scottish Isles. The paper was published in Scientific Reports. To read more visit:Characterisation of pharmacogenomic variation in the Shetland and Orkney Isles in Scotland This article was published on 2025-12-01
