In a momentous landmark for medical research, UK Biobank has today [Thursday 30 November] unveiled incredible new data from whole genome sequencing of its half a million participants. This is set to drive the discovery of new diagnostics, treatments and cures and, uniquely, is available to approved researchers worldwide, via a protected database containing only de-identified data (e.g. name, address, date of birth, name of GP and more stripped out). This abundance of genomic data is unparalleled, but what cements it as a defining moment for the future of healthcare is its use in combination with the existing wealth of data UK Biobank has collected over the past 15 years on lifestyle, whole body imaging scans, health information, and proteins found in the blood.
After five years, more than 350,000 hours of genome sequencing, and over £200 million of investment, UK Biobank is releasing the world's largest-by-far single set of sequencing data, completing the most ambitious project of its kind ever undertaken. "This is a veritable treasure trove for approved scientists undertaking health research, and I expect it to have transformative results for diagnoses, treatments and cures around the globe," said Professor Sir Rory Collins FRS FMedSci, Principal Investigator at UK Biobank.
Set up 20 years ago, the charity UK Biobank recruited half a million altruistic volunteers to create the world's most comprehensive source of health data. It is used by researchers across the world, from academic, commercial, government and charitable settings, for scientific discoveries that improve human health.
UK Biobank now provides the most detailed picture of human health that exists, equipping researchers with the ultimate toolbox to make previously out-of-reach links and discoveries about disease development possible. "The sheer amount of genetic data is exceptional – it is twice as much as anywhere else – but UK Biobank's data is so illuminating because we've been able to follow the health of our brilliant volunteers for around 15 years," continued Professor Collins.
Game-changing data for health research
Today's addition of sequencing data comes after a series of great leaps made using the vast UK Biobank biomedical database. These leaps include: finding genes associated with protection against obesity and type 2 diabetes, which has the potential to lead to the development of new drugs; identifying individuals at very high genetic risk for diseases such as heart disease, breast cancer and prostate cancer, which may help with screening; and a link between activity and Parkinson's that can predict the disease up to seven years before diagnosis from smartwatch data, potentially leading to early intervention. The new sequencing data will dramatically enhance the existing data's potential.
Whole genome sequencing data on this scale, combined with UK Biobank's existing data and biological samples, will result in extraordinary biomedical innovations, including:
- More targeted drug discovery and development. Experimental therapeutics that are developed based on evidence from human genetics are twice as likely to be approved for clinical use. "This landmark dataset will enable us to leverage the power of artificial intelligence and machine learning for rapidly identifying novel disease targets and helping researchers predict how a candidate medicine might impact certain subpopulations of patients, based on their genetics. This could pave the way for more efficient clinical development and drive progress toward precision medicine," said John Reed, M.D., Ph.D., Executive Vice President for Innovative Medicine R&D at Johnson & Johnson.
- Discovering thousands of disease-causing non-coding genetic variants. Little is known about 98% of the human genome, once erroneously called 'junk DNA'. This is the portion of DNA that doesn't code for proteins and already, using earlier sequencing data, a study has found examples from this region where rare variants are associated with specific genetically-determined characteristics.
- Accelerating precision medicine. With a sample size of half a million people, and data collected on over 10,000 variables (such as blood pressure, cognitive function, diet and bone density), researchers using UK Biobank are driving tailored healthcare, such as investigating why people with the same genetic predisposition for a disease have different outcomes, reactions and side-effects to the same treatment.
- Understanding the biological underpinnings of disease. For many illnesses, such as Parkinson's, Alzheimer's and autoimmune diseases, the underlying origins are poorly understood. "This ground-breaking dataset allows scientists to explore how genetics affect levels of proteins, metabolites and other physiological factors, more closely than ever before, promising to accelerate our understanding of the genetic underpinnings of disease," said David Reese, Executive Vice President R&D, Amgen.
"It is an honour to represent UKRI during this landmark event for science, following our support of UK Biobank since its conception. Researchers can now apply to access de-identified full genome data from half a million participants, alongside a rich combination of medical, biochemical, lifestyle and environmental data from volunteers involved.
"Today marks an important milestone in UKRI's commitment to realise the potential of genetics for biomedical research, innovation and translation to the clinic," said Professor Dame Ottoline Leyser DBE FRS, Chief Executive of UK Research and Innovation (UKRI).
Democratizing data
To date, over 30,000 researchers from more than 90 countries have registered to use UK Biobank, with over 9,000 peer-reviewed papers published as a result. Researchers are given the tools and computing power to analyse the de-identified data via UK Biobank's secure, cloud-based Research Analysis Platform.
"From the sequencing of the genomes themselves through to innovative and secure data storage, the release of this rich dataset marks a significant and impressive moment in scientific research. It's truly field-opening for understanding the interactions between our genetics, environment and health.
"Wellcome's funding has supported a new, bespoke data platform that will provide approved researchers with the tools they need to analyse the wealth of data. Crucially, this opens up exciting opportunities for early-career researchers and those in low-and-middle-income countries, in turn offering huge potential to unlock new discoveries and enhance our understanding of health to improve lives around the world," said Cheryl Moore, Chief Research Programmes Officer, Wellcome Trust.
The consortium behind this joint venture
This project was funded by Wellcome, UKRI and four biopharmaceutical companies; Amgen, AstraZeneca, GSK and Johnson & Johnson5. "This world-leading project has only been possible due to the collaboration between industry, charity and Government, who have worked together to enable the sequencing of 500,000 genomes. It showcases the importance of partnership and working together to push boundaries and enhance our scientific knowledge to support the development of future medicines for patients around the world," said Sharon Barr, Executive Vice President BioPharmaceuticals R&D from AstraZeneca.
"UK Life Sciences are going from strength to strength, and UK Biobank is leading the way by combining world-leading data, fantastic infrastructure, brilliant minds and cross-sector collaboration," added Professor Sir John Bell CH GBE FRS FMedSci.
In return for significant investment, UK Biobank gives nine months' exclusive data access to industry members of the consortium. In this way, commercial companies invest heavily to enhance a ground-breaking health dataset that is then available to approved research across the world. "Bringing together science and technology to deepen our understanding of patients, human biology, and disease mechanisms is a key part of the discovery and development of new medicines, and the work of UK Biobank has been central to our approach. There is no other resource like it that combines genetic, biological and clinical data and then makes those data available to researchers across the industry with the goal of improving health. The partnership across the UK life sciences ecosystem has been critical to make this all possible," said Robert Scott, Vice President, Human Genetics, from GSK.
The DNA sequencing was completed by Amgen's subsidiary, deCODE Genetics, and the Wellcome Sanger Institute, using Illumina NovaSeq technology, and with deCODE providing additional informatics processing support.
This data – and the rest of UK Biobank's de-identified data – is now globally accessible for approved researchers on the UK Biobank Research Analysis Platform which is hosted on Amazon Web Services (AWS) in the London region and enabled by DNAnexus. This is the first time a globally accessible resource, the computing power, and necessary storage required to analyse this size and sort of data, has been made available to researchers.
Following completion of the sequencing, the industry consortium led efforts to process and joint call the genomes using the DRAGEN pipeline on AWS infrastructure, enabling this vast volume of data to be transformed into a single combined genetic dataset by Illumina. These outputs further enrich the scientific importance of the data, enhancing the potential to identify less frequent genetic variants and making it more cross-comparable with other large scale population health studies.
The four pharmaceutical companies plan to publicly share their summary statistical analyses arising from the consortium collaboration, including genome-wide association results, providing the research community with highly valuable insights without the costly and time-consuming burden of analysing raw data.
Leveraging genetic variations for more effective cancer therapies