Our genomic future
Three experts consider the direction of travel for genomics — and the projects that will help us get there
Picture this: It’s 2070. You’re sitting with your GP following some blood tests. She pulls up a report to discuss with you. Using the results of your blood tests, as well as information from your whole genome sequence (which was taken at birth as is now routine practice), scientists have compiled a personalised report detailing not only your results, but your risk of deterioration and a bespoke treatment plan involving a drug that is only suitable for 20% of the population. It’s also recommended as a preventative measure for one of your three children, who currently has no symptoms.
Far-fetched? The body of evidence required for such drastic changes to our healthcare might be growing faster than you think. In this article, we hear from three experts involved in pioneering genomics projects that might mean change is right around the corner.
Integrated risk scores
Eyes in the healthcare world light up at the prospect of using integrated risk scores, a tool that allows us to aggregate a person’s risk of certain conditions based on a combination of genomic and non-genomic information. Dr Cosima Gretton explains: “Many serious health conditions such as heart disease, cancer and diabetes are influenced by multiple genetic variants in an individual’s DNA. Each of these variants contribute a small amount to risk that can in theory be calculated and then used in combination with information about other important variables, such as age, sex or environmental factors, to indicate a person’s future risk of disease.”
It is arguably the potential for prevention that has people excited. But, as Dr Gretton explains, “there is much research needed to determine the clinical validity, utility and cost effectiveness of using integrated risk scores in healthcare.” Cue the UK’s largest ever health research programme, Our Future Health, where Dr Gretton works as executive director of digital health and deputy chief medical officer. “There is potential for integrated risk scores to enable a more preventative approach, but there are many unknowns, so our goal is to enable researchers to generate the evidence needed.”
The programme aims to recruit five million volunteers. “The goal is to create one of the most detailed pictures ever of people’s health,” Dr Gretton says. “The scale of Our Future Health will allow researchers to generate evidence — taking into account clinical, health, psychological, behavioural, social and economic factors — that will help us understand the impact of giving people personalised health and risk information. This will aid decision making when it comes to whether and how the scores should be implemented at scale, providing us with a stronger basis for future health policy decisions.”
“Our Future Health also provides an important opportunity to look at the use of integrated risk scores for younger adults,” Dr Gretton adds. “Diabetes and cardiovascular disease risk scores, for example, are currently only offered systematically to adults over the age of 40. Exploring whether this is the right approach is particularly relevant for people from some ethnic groups, such as South Asians, in whom diabetes and heart disease typically develop at a younger age. So we aim to be able to better assess risk for people who have previously been underrepresented in research.”
Newborn screening
“About 1 in 17 people in the UK is affected by a rare condition at some point in their lifetime. And yet, for too many people, it’s a long road to diagnosis,” says Genomics England clinical fellow Dr Katrina Stone. “Genomic newborn screening has the potential to change that; to eliminate delays in diagnosis meaning treatments can be started earlier when they are often more effective.”
Genomics England’s Generation Study is a pioneering project that plans to sequence the genomes of 100,000 babies. Clinical care will be delivered within the NHS: “If one of the conditions screened for is suspected, the family will receive their result from an NHS specialist, thus entering routine care.” Evidence gathered during the course of the study will be used to “consider the role of genomic sequencing alongside other forms of newborn screening, helping to define the capabilities and limitations of newborn genomic sequencing and informing future policy.” Meanwhile de-identified genomic and linked healthcare data will be shared with a pool of approved researchers aiming to make new links between our genes and health.
Beyond its immediate benefits, the study has lofty aims. “In the short term, participating babies will be screened for over 200 rare conditions for which there is currently a recommended treatment or intervention. In the longer term, the evidence gathered from the study will help us build a clearer picture of the potential role for genomic sequencing at birth.” Dr Stone continues, “the study is the only one of its kind that is taking place within a national healthcare service. This context gives us a unique vantage point from which to consider not only what role genomic sequencing could play in early intervention in childhood-onset conditions, but also the potential benefit of having access to a person’s genomic information over their lifetime and what implications this may have for their ongoing healthcare.”
Read more about the Generation Study in our GeNotes resource.
Pharmacogenomics
We can describe pharmacogenomics as the way in which “our genetics impacts our response to medicines,” says NIHR academic clinical lecturer and clinical genetics specialty registrar Dr John McDermott. Pharmacogenomic testing is currently used in the NHS, however, “it’s done in a reactive way: patient presents, you do the test, you get the results, then you change prescription around that particular indication. It’s being done at the moment for a small number of genes.”
In the near future, Dr McDermott is hopeful that we may move towards panel-based testing. “This means that, rather than just looking at a single gene, you’re looking at multiple genes and genetic variants all at the same time. The challenge behind that isn’t so much the genetics – panel testing is cheap, rapid and we can do that now in our labs – it’s how we integrate the resulting data within healthcare records.” In fact, how to integrate genomic data into a patient’s record, in a way that can understood by the attending clinician and be acted on then and there, is a very real and ongoing challenge. It’s something NHS England’s newly formed Pharmacogenomics and Medicines Optimisation hopes to tackle. “You can’t just give clinicians a PDF!” he jokes, adding, “we’ve found that just won’t work.”
What sort of practice will be impacted by pharmacogenomics? “It’s going to impact everybody,” explains Dr McDermott. “There are not enough clinical geneticists or clinical pharmacologists in the country to see all these patients, so it is going to have to become part of routine practice.” He remains realistic: “Pharmacogenomics isn’t a panacea; it’s about bringing in other patient variables (for example, other medicines they’re on, their age, etc) to make the best decision for that patient. It’s a really exciting field to work in.”
Want to learn more about pharmacogenomics? Get started with this short introduction in GeNotes.
