Our research shows that those at high genetic risk of obesity will need personalised support to help them stay at, or return to, a healthy weight.
OXFORD, UK, 8 November 2024. Genomics today announced new research which suggests knowledge of genetic risk could help address obesity, a major public health challenge, based on a study of the UK Biobank and ALSPAC populations. The findings were presented at the American Society of Human Genetics (ASHG) Annual Meeting 2024. They indicate that genetic information can identify individuals who are more likely to progress to obesity later in life, and suggest that those at high risk may require tailored personalised prevention support based on their genetic profile.
In the UK, nearly two-thirds of adults are overweight or obese, and obesity is estimated to cost the health system £11 billion a year, with the total cost to society estimated at £98 billion per year.[1] Being overweight is defined as having a Body Mass Index (BMI) of over 25, and being obese as BMI over 30. This preventable disease increases people’s risk of type 2 diabetes, heart disease, stroke, cancer, and mental ill health, amongst others. Prevention of obesity and related complications is a major challenge for healthcare systems around the world, who would benefit from identification of individuals with the highest risk of weight gain to provide greater support; particularly with the introduction of novel therapeutic weight loss treatments.
The study found that amongst young adults aged 26-34 with healthy weight (BMI under 25), those with a genetic risk score for high BMI were 10 times more likely to develop obesity in midlife (46-54 years), than those genetically predisposed to have low BMI.[2] The genetic risk score was calculated using Genomics’ proprietary polygenic risk scores (PRS).
The research also indicates that unhealthy lifestyles affect those with high genetic risk more than those with lower genetic risk. For example, comparing the BMI of 24 year old women with high and low genetic risk, the difference was, on average, four times larger for those with unhealthy lifestyles in childhood (lower activity levels and higher calorie intake), compared to who had healthy lifestyles in childhood (higher activity levels and lower calorie intake).
This supports previous studies which have shown that the impact of PRS is substantially greater in individuals with unhealthy lifestyles in adulthood[3] and that standard lifestyle advice, including on calorie intake and activity levels, is likely to be ineffective: an individual with PRS at the 95th percentile would need to walk about 10,000 steps more per day than someone at the 20th percentile to maintain a stable BMI.[4]
By identifying individuals in childhood or early adulthood who are most likely to transition to obesity in midlife, this provides a window for patient-centric, science-led approaches, to avoid complications of obesity.
"Obesity and overweight puts over 60% of adults in the UK at an increased risk of serious complications, such as heart disease, type 2 diabetes and cancer”, said Professor Sir Peter Donnelly, Founder and CEO of Genomics.
“Genetic risk scores are the essential missing piece of the puzzle in addressing one of the greatest public health challenges of our time.
"Our research shows that those at high genetic risk of obesity will need personalised support to help them stay at, or return to, a healthy weight.
"It is clear from these studies that prevention advice and public health initiatives which take into account genetic profiles would be significantly more effective in helping people stay healthier for longer.
“Based on genetics, some of us will need much more support and help than others to maintain a healthy weight, and it is critical that our prevention and treatment programmes recognise this.”
Genomics’ single genetics test provides risk prediction for major preventable diseases. The company has successfully completed a trial in the NHS, incorporating the genetic element of risk for cardiovascular disease into the NHS Health Checks. Genomics’ PRS for multiple diseases will also be fed back to the millions of participants of the flagship Our Future Health programme in the coming years, which to date has over one million people enrolled.[5] Last week, Genomics announced its first health insurance partnership in the UK at the Bupa Health Symposium 2024, where its tests are used as part of health assessments for Bupa customers across the UK. Genomics partners with life science organisations, and health systems across the UK and the US.
Genomics has established offices in Oxford, Cambridge, London, and Cambridge, Massachusetts.
ENDS
About the study
Genomics plc, 2024: “The role of genetics in predicting progres sion to severe obesity in midlife”
Leveraging data from 1,365,965 individuals, Genomics developed and optimised a multi-ancestry polygenic risk score (PRS) for body mass index (BMI). Using UK Biobank, we identified an independent testing subset of 3,953 individuals with BMI measured both in early adulthood (26 - 34 years, before recruitment to UK Biobank) and midlife (46 - 54 years, after recruitment to UK Biobank), and evaluated if PRS could predict transitions across BMI categories, relevant to clinical practice. For individuals in the top 5% of the PRS distribution (high), the risk of transitioning from healthy weight (BMI less than 25) to obesity (BMI greater than 30) was 20.87% (95% CI 16.56%-25.73%), compared to 2.18% (95% CI 0.88%-4.44%) for those in the bottom 5%. On average, individuals with a high PRS (top 5%) experience a BMI increase from their 20’s to late middle age which is more than 2.2-fold higher than those with a low PRS (bottom 5%) .
In the study, high calorie consumption in childhood is defined as 1900 calories. Low calorie consumption is defined as 1400 calories. High activity levels are defined as 4 instances of vigorous activity per week, and low activity levels as fewer than 4 instances.
About UK Biobank[6]
UK Biobank is a large-scale biomedical database and research resource containing de-identified genetic, lifestyle and health information and biological samples from half a million UK participants.
It is the most comprehensive and widely-used dataset of its kind, and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.
About ALSPAC[7]
Based at the University of Bristol, Children of the 90s, also known as Avon Longitudinal Study of Parents and Children (ALSPAC), is a world-leading birth cohort study.
About Genomics
Genomics is a pioneering healthcare company that uses large-scale genetic information to develop innovative precision healthcare tools and bring new understanding to drug discovery. We were formed in 2014 by four world-leading statistical and human geneticists at the University of Oxford. Today, we are collaborating with some of the world’s leading healthcare organisations and helping them to predict, prevent, treat, and cure—dramatically reducing the human and financial cost of common diseases like cancer, diabetes, and heart disease.
Media contact
Zuzanna Grzeskiewicz, Director of Communications, Genomics
Teneo, on behalf of Genomics plc
genomics@teneo.com
[1] Tony Blair Institute for Global Change. November 2023. Unhealthy Numbers: The Rising Cost of Obesity in the UK. Available at: https://institute.global/insights/public-services/unhealthy-numbers-the-rising-cost-of-obesity-in-the-uk Last accessed November 2024
[2] Genomics plc. November 2024. The clinical benefits of genetically guided population health management. Poster presented at ASHG 2024.
[3] Kim et al. 2024. Cell Metabolism. Association of genetic risk, lifestyle, and their interaction with obesity and obesity-related morbidities. Available at: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00229-8 Last accessed November 2024
[4] Brittain et al. 2024. JAMA. Physical Activity and Incident Obesity Across the Spectrum of Genetic Risk for Obesity. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10973894/ Last accessed November 2024
[5] Our Future Health. October 2024. Our Future Health becomes world’s largest research programme of its kind. Available at: https://ourfuturehealth.org.uk/news/our-future-health-becomes-worlds-largest-research-programme-of-its-kind/ Last accessed November 2024
[6]UK Biobank. https://www.ukbiobank.ac.uk/ Last accessed November 2024
[7]University of Bristol. About ALSPAC. https://www.bristol.ac.uk/alspac/about/#:~:text=Based%20at%20the%20University%20of,world%2Dleading%20birth%20cohort%20study. Last accessed November 2024