"Improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses – including cancer, heart diseases, stroke, diabetes, arthritis, osteoporosis, eye disorders, depression and forms of dementia."
UK Biobank is a large long-term biobank study in the United Kingdom (UK) which is investigating the respective contributions of genetic predisposition and environmental exposure (including nutrition, lifestyle, medications etc.) to the development of disease. It began in 2006.[1][2][3][4] UK Biobank has been cited as an important resource for cancer research.[5]
The study is following about 500,000 volunteers in the UK, enrolled at ages from 40 to 69. Initial enrollment took place over four years from 2006, and the volunteers will be followed for at least 30 years thereafter.[12]
Prospective participants were invited to visit an assessment centre, at which they completed an automated questionnaire and were interviewed about lifestyle, medical history and nutritional habits; basic variables such as weight, height, blood pressure etc. were measured; and blood and urine samples were taken. These samples were preserved so that it was possible to later extract DNA and measure other biologically important substances. During the whole duration of the study it was intended that all disease events, drug prescriptions and deaths of the participants are recorded in a database, taking advantage of the centralized UK National Health Service.[13][14]
During the initial physical examination, basic feedback was provided to the participant regarding their weight, height, BMI, blood pressure, lung vital capacity, bone density and intra-ocular pressure; however if any other medical problems were detected, neither the participant nor their physician would be notified. Problems detected later, such as genetic risk factors, were not conveyed to either participant or physician ("to ensure that volunteers are not penalised by insurance companies, for example, which may require customers to disclose the results of any genetic tests.").[15]
From 2012, researchers were able to apply to use the database (though they are not given access to the volunteers, who will remain strictly anonymous). A typical study using the database might compare a sample of participants who developed a particular disease, such as cancer, heart disease, diabetes or Alzheimer's disease, with a sample of those that did not, in an attempt to measure the benefits, risk contribution and interaction of specific genes, lifestyles, and medications.
In 2017 researchers were able to access the database including genetic information.[16][17] By 2017 Biobank participants had approximately 1.3 million hospitalisations, 40,000 cancer incidents with 14,000 of them having died.[18]
Development
An incremental approach was adopted to developing the study procedures and technology, using systems designed and developed by the Clinical Trial Service Unit. This consisted of a series of pilot studies of increasing complexity and sophistication with interludes for assessment of results and additional scientific input. In-house trials were conducted during 2005, and a fully integrated clinic was run at Altrincham, Greater Manchester throughout Spring 2006 where 3,800 individuals were assessed. On 22 August 2006 it was announced that the main programme would recruit men and women aged between 40 and 69 based from up to 35 regional centres,[19] however recruitment proved more efficient than hoped and only 22 centres had been opened when the recruitment target of 500,000 was reached in 2010.
Initial information collected
The study was initially launched with a visit consisting of the following:[18]
The UK Biobank project operates within the terms of an Ethics and Governance Framework.[20][21][22] The Framework describes a series of standards to which UK Biobank will operate during the creation, maintenance and use of the resource and it elaborates on the commitments that are involved to those participating in the project, researchers and the public more broadly. The independent UK Biobank Ethics and Governance Council provides advice to the project and monitors its conformity with the Framework.[23] The Council also advises more generally on the interests of research participants and the general public in relation to the project.[citation needed]
Following the initial pilot stage in the 2005-6 period, the main study began in April 2007 and by the end of that year 50,000 people had taken part. Recruitment reached 100,000 in April 2008, 200,000 in October 2008, 300,000 in May 2009, 400,000 in November 2009 and passed the 500,000 target in July 2010. Participant enrollment was declared complete in August 2010.[25] The volunteers were largely healthy, wealthy and white European. Rather than recruiting more participants into the biobank, the organisation is helping other institutions establish and run similar initiatives.[26]
Usage
The UK Biobank dataset was opened to applications from researchers in March 2012.[27] The resource is available to scientists from the UK and outside, whether they work in the public or private sector, for industry, academia or a charity, subject to verification that the research is health-related and in the public interest. Researchers are required to publish their results in an open source publication site or in an academic journal and return their findings to the UK Biobank.[18] By April 2017 4,600 researchers had registered to use the resource, over 880 applications had been submitted[28] and 430 research projects were completed or underway. 130 peer-reviewed articles based on the UK Biobank data had been published by January 2017.[18][29]
Extensions
Since the completion of recruitment several new types of data have been added:
During 2011-12 participants who supplied an email address were asked to assist by completing web-based dietary questionnaires, with the aim of combining a series of daily 'snapshots' to form a picture of overall nutrition. 176,012 of the participants responded at least once and 27,535 completed four questionnaires over a 16-month period.[18]
During 2012–13 25,000 participants at the Stockport centre were asked to attend the assessment centre to repeat the initial measurements. It was intended to repeat these assessments every few years.[18]
In 2013 to 2015, Axivity AX3 tri-axial wrist physical activity monitors were distributed to 100,000 participants, which recorded week-long triaxial acceleration at 100Hz.[30][31] This data was centrally processed, and listed on the Data Showcase.[32][33]
In 2014 and 2015 120,000 participants completed a questionnaire on cognitive functions. Four of the tests were repeats of the initial assessment and two tests (symbol digit substitution and trail making) were new.[18]
In 2015 and 2016, 117,500 participants completed questionnaires on occupational history and related medical information.[18]
In 2016 and 2017 137,400 participants completed questionnaires on mental health events including subjective well-being estimates, psychotic experiences, self-harm behaviours, traumatic events and cannabis and alcohol use.[18]
A genomic assay of 820,967 SNPs was conducted on the participants blood samples. Data from an initial 150,000 participants were released in 2015, the remainder in July 2017,[34][17] and the first results in October 2018.[35][36]
Information from UK registries of death (from 2006) and cancer (Scotland from 1957, England and Wales from 1995) were linked to the main Biobank dataset on an ongoing basis.[18]
Data from NHS hospital inpatient records (England from 1996, Scotland from 1997 and Wales from 1998) were linked to the main dataset on an ongoing basis.[18]
In 2019 exome sequence data from 50,000 persons was released, with 200,000 being available by 2020.[37]
In 2020 20,000 volunteers agreed to collect and send a monthly blood sample for analysis of SARS-CoV-2 antibodies. They included existing Biobank participants and their children and adult grandchildren living in separate households.[38]
In 2021 NMR metabolomic data on approximately 121,000 persons was released.[39]
In June 2021 a subset of volunteers who had acknowledged that they had already received at least their first Covid-19 vaccine dose, were asked to participate in a study to determine if their Covid-19 antibodies were as a result of their vaccination or from a prior infection.
Findings
Reviews of UK Biobank data have found that pescatarians and vegetarians have a lower risk of colorectal and prostate cancer compared to red meat eaters.[40] Consumption of processed meat increases risk of breast cancer.[41] They have also found that men with higher total and central adiposity have an increased risk of prostate cancer death.[42]
A 2022 review of UK Biobank data found that road traffic noise exposure increases risk of CVD mortality, stroke and all-cause mortality.[43] A 2023 review found that participants with sense of meaning and purpose in life have a decreased risk of dementia.[44]
Ongoing developments
In 2018 a number of projects were underway to generate additional data:
A set of additional assays on the blood and urinary samples were being conducted in 2016 and 2017[18] with blood results expected to be released in Q4/2018.
A new type of assessment centre opened in 2014 to collect imaging data. The visits extended the initial dataset to include magnetic resonance imaging (MRI) scans of brain[45][46][47][48] heart and abdomen, as well as neck-to-knee volumetric MRI scans, whole body dual-energy X-ray absorptiometry (DXA) scan of bones and joints, ultrasound measurements of the carotid arteries and resting 12-lead electrocardiogram (ECG). Initial data on 4,000 participants was released at the end of 2015 and by mid-2018 over 25,000 participants had been scanned. It is planned to scan 100,000 participants by 2022, and to do additional repeat scans on 10,000 of these 2–3 years later.[18]
A subset of 2500 participants are being asked to repeat the Activity Study at quarterly intervals for a year to gauge the size of seasonal effects.
In 2018 there were several plans, either provisional or underway, for enhancing the resource:
Primary care data (such as referrals, diagnoses and prescriptions) were planned to be made available in 2018–2019.[18]
Linking data from NHS hospital outpatient records and GP to the main dataset were being investigated in 2018.[18]
Linkages to disease-specific registries and screening programs were also being investigated in 2018.[18]
Exome sequencing is underway with the first batch of 50,000 sequences due to be released in mid-2019.
Full genome sequencing was being investigated with a pilot project underway.
Opinion
The project has been generally praised for its ambitious scope and unique potential. A scientific review panel concluded, the "UK Biobank has the potential, in ways that are not currently available elsewhere, to support a wide range of research".[25]Colin Blakemore, chief executive of the MRC, predicted it "will provide scientists with extraordinary information"[19] and "grow into a unique resource for future generations."[25]
There was some early criticism, however. GeneWatch UK, a pressure group that claims to promote the responsible use of genetic information, asserted that the complexity of the programme could result in the finding of "false links between genes and disease",[25] and expressed concern that the genetic information from patients could be patented for commercial purposes. Biobank's chief executive described such a risk as "extremely low, if it exists at all."[19]
Some literature has raised concerns that the UK Biobank is not representative of the diversity of the UK population or is not applicable to diverse populations.[49][50]
Funding
The UK Biobank is funded by the UK Department of Health, the Medical Research Council, the Scottish Executive, and the Wellcome Trust medical research charity. The cost of the initial participant recruitment and assessment phase was 62 million GBP.[51]
Related projects
EPIC (European Prospective Investigation into Cancer and Nutrition) is a similar study that was started in 1992 and involves 520,000 men and women mostly between 35 and 70 years old from ten European countries. Participants are recontacted every three to five years. It is specifically designed to study the respective roles of diet and genes in the development of cancer.[13][52]
In 1996, Icelandic neurologist Kári Stefánsson founded a private company deCODE genetics, to assemble genealogical, genomic and health data from across the population of Iceland – then about 270,000 people.[53] The purpose was to mine this data, under encrypted identifiers generated by the country's Data Protection Authority,[54] to identify genetic variations associated with diseases[55] and to use that information to develop new drugs.[56] As of 2018, more than 160,000 people had contributed DNA and detailed health information to the company's research into the inherited components of common and rare diseases.[57] deCODE has published hundreds of discoveries in cardiovascular and autoimmune diseases, Alzheimer's and other central nervous system diseases, many types of cancer, and dozens of other conditions and traits.[58] Now an independent subsidiary of Amgen,[59] deCODE has provided novel targets now in clinical development and provides human genetics validation across a range of therapeutic areas.[60] In 2018, Stefansson made good on a promise that the company would launch a website that enables Icelanders to request the analysis of their sequence data to determine whether they carry a SNP in the BRCA2 gene that has been linked in Icelanders to significantly increased risk of breast and prostate cancer.[61] More than 10% of the population has used this portal, and the country's national health system has increased clinical testing, counseling and treatment to take advantage of this information for public health.[62]
The Estonian Genome Project was started in 2000 with the aim of improving public health in the country.[63] Initially it was hoped to obtain biological samples and health data from 70% of the 1.4 million population of Estonia.[64] The aims of the project were downsized however over the years. By the end of 2019 Estonian Genome Project had recruited 200 000 gene donors i.e. 20% of the adult population.[65]
The China Kadoorie Biobank study collected questionnaire and physical data and blood samples on 510,000 men and women aged between 30 and 79 from 10 regions in China between 2004 and 2008 with the aim of investigating chronic diseases (e.g. heart attack, stroke, diabetes, and cancer). Participants have been linked to mortality registers and nationwide health systems and a sub-group of 25,000 are retested every few years.[66][18]
In 2006, a similar project by the U.S. National Human Genome Research Institute known as "The American project" was proposed.[15] In 2015 the US National Institutes of Health launched the "Precision Medicine Initiative" which was renamed "All of Us" in 2016.[67] This project had enrolled over 10,000 people by January 2018 in a pilot phase with an aim to sign up one million participants by 2022.[68] As of February 2021 the program has enrolled 369,000 participants with 235,000 Electronic Health Records and 280,000 biosamples.[67][69]
The Lifelines cohort study was started in 2006 and collects data and samples on 167,000 children, adults and elderly from the Northern part of the Netherlands. The aim of Lifelines is to constitute a biobank that provides high-quality data and samples by following all participants over a period of at least 30 years.[70][71] The collected data offer excellent opportunities for studies worldwide unraveling the etiology of multifactorial diseases focusing on multifactor risk factors. This will help to move forward to more personalised health care and prevention and to answer the question why some people grow old in good health while others contract diseases.[citation needed]
The Finngen project was launched in 2018 with the aim of collecting biological samples from 500,000 participants in Finland over six years with the aim of improving health through genetic research.[72]
Epidemiology is the study and analysis of the distribution, patterns and determinants of health and disease conditions in a defined population.
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or through biochemical analysis to measure specific protein output. In a medical setting, genetic testing can be used to diagnose or rule out suspected genetic disorders, predict risks for specific conditions, or gain information that can be used to customize medical treatments based on an individual's genetic makeup. Genetic testing can also be used to determine biological relatives, such as a child's biological parentage through DNA paternity testing, or be used to broadly predict an individual's ancestry. Genetic testing of plants and animals can be used for similar reasons as in humans, to gain information used for selective breeding, or for efforts to boost genetic diversity in endangered populations.
A cohort study is a particular form of longitudinal study that samples a cohort, performing a cross-section at intervals through time. It is a type of panel study where the individuals in the panel share a common characteristic.
The Women's Health Initiative (WHI) was a series of clinical studies initiated by the U.S. National Institutes of Health (NIH) in 1991, to address major health issues causing morbidity and mortality in postmenopausal women. It consisted of three clinical trials (CT) and an observational study (OS). In particular, randomized controlled trials were designed and funded that addressed cardiovascular disease, cancer, and osteoporosis.
Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on their predicted response or risk of disease. The terms personalized medicine, precision medicine, stratified medicine and P4 medicine are used interchangeably to describe this concept though some authors and organisations use these expressions separately to indicate particular nuances.
A nested case–control (NCC) study is a variation of a case–control study in which cases and controls are drawn from the population in a fully enumerated cohort.
Genetic discrimination occurs when people treat others differently because they have or are perceived to have a gene mutation(s) that causes or increases the risk of an inherited disorder. It may also refer to any and all discrimination based on the genotype of a person rather than their individual merits, including that related to race, although the latter would be more appropriately included under racial discrimination. Some legal scholars have argued for a more precise and broader definition of genetic discrimination: "Genetic discrimination should be defined as when an individual is subjected to negative treatment, not as a result of the individual's physical manifestation of disease or disability, but solely because of the individual's genetic composition." Genetic Discrimination is considered to have its foundations in genetic determinism and genetic essentialism, and is based on the concept of genism, i.e. distinctive human characteristics and capacities are determined by genes.
In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.
A biobank is a type of biorepository that stores biological samples for use in research. Biobanks have become an important resource in medical research, supporting many types of contemporary research like genomics and personalized medicine.
A prospective cohort study is a longitudinal cohort study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome. For example, one might follow a cohort of middle-aged truck drivers who vary in terms of smoking habits, to test the hypothesis that the 20-year incidence rate of lung cancer will be highest among heavy smokers, followed by moderate smokers, and then nonsmokers.
Generation Scotland is a biobank, a resource of biological samples and information on health and lifestyle from thousands of volunteer donors in Scotland.
The Trøndelag Health Study is a cohort health study performed in the Norwegian county of Trøndelag. HUNT is considered one of the most extensive cohort studies ever conducted in any country. The HUNT Research Centre, which is responsible for collecting and providing access to the data and samples from the study, is part of the Faculty of Medicine and Health Sciences at the Norwegian University of Science and Technology (NTNU).
The Africa/Harvard School of Public Health Partnership for Cohort Research and Training launched in 2008, is a collaborative research project led by Principal Investigators, Dr. Hans-Olov Adami and Dr. Michelle D. Holmes. Together with research scientists, Dr. Shona Dalal and Dr. Todd G. Reid, this team represents the Harvard Coordinating Site of the Partnership with colleagues from five institutions in Nigeria, South Africa, Tanzania, and Uganda. The Africa/HSPH PaCT project plans on investigating the association of lifestyle factors and chronic disease risk in sub- Saharan Africa, through a large epidemiological cohort study that will include approximately 500,000 participants. Africa/HSPH PaCT is the first and largest cohort study conducted in sub-saharan Africa to employ mobile phone technology to follow participants and collect data. Africa/HSPH PaCT will also provide the infrastructure for capacity-building and for training a new generation of health professionals.
Biobank ethics refers to the ethics pertaining to all aspects of biobanks. The issues examined in the field of biobank ethics are special cases of clinical research ethics.
CARTaGENE is a population based cohort based on an ongoing and long-term health study of 40, 000 men and women in Québec. It is a regional cohort member of the Canadian Partnership for Tomorrow's Health (CanPath). The project's core mandate is to identify the genetic and environmental causes of common chronic diseases affecting the Québec population. The overall objective from a public health perspective is to develop personalized medicine and public policy initiatives targeting high-risk groups. CARTaGENE is under the scientific direction of Sébastien Jacquemont, Ekaterini Kritikou, and Philippe Broët of the Sainte-Justine Children's Hospital University Health Center. Based in Montréal Québec, Canada, CARTaGENE is operated under the infrastructure of the Sainte-Justine Children's Hospital University Health Center and has seen funding from Genome Canada, the Canadian Foundation for Innovation and Génome Québec and the Canadian Partnership Against Cancer (CPAC) since 2007 among other sources. The program was initially founded by Professors Claude Laberge and Bartha Knoppers, and developed through two phases of participant recruitment under the direction of Professor Philip Awadalla as Scientific Director of the cohort from 2009 to 2015, who is now the National Scientific Director of the Canadian Partnership for Tomorrow's Health (CanPath).
Dynamic consent is an approach to informed consent that enables on-going engagement and communication between individuals and the users and custodians of their data. It is designed to address the many issues that are raised by the use of digital technologies in research and clinical care that enable the wide-scale use, linkage, analysis and integration of diverse datasets and the use of AI and big data analyses. These issues include how to obtain informed consent in a rapidly-changing environment; growing expectations that people should know how their data is being used; increased legal and regulatory requirements for the management of secondary use of data in biobanks and other medical research infrastructure. The approach started to be implemented in 2007 by an Italian group who introduced the ways to have an ongoing process of interaction between researcher and participant where "technology now allows the establishment of dynamic participant–researcher partnerships." The use of digital interfaces in this way was first described as 'Dynamic Consent' in the EnCoRe project. Dynamic Consent therefore describes a personalised, digital interface that enables two-way communication between participants and researchers and is a practical example of how software can be developed to give research participants greater understanding and control over how their data is used. It also enables clinical trial managers, researchers and clinicians to know what type of consent is attached to the use of data they hold and to have an easy way to seek a new consent if the use of the data changes. It is able to support greater accountability and transparency, streamlining consent processes to enable compliance with regulatory requirements.
DNA encryption is the process of hiding or perplexing genetic information by a computational method in order to improve genetic privacy in DNA sequencing processes. The human genome is complex and long, but it is very possible to interpret important, and identifying, information from smaller variabilities, rather than reading the entire genome. A whole human genome is a string of 3.2 billion base paired nucleotides, the building blocks of life, but between individuals the genetic variation differs only by 0.5%, an important 0.5% that accounts for all of human diversity, the pathology of different diseases, and ancestral story. Emerging strategies incorporate different methods, such as randomization algorithms and cryptographic approaches, to de-identify the genetic sequence from the individual, and fundamentally, isolate only the necessary information while protecting the rest of the genome from unnecessary inquiry. The priority now is to ascertain which methods are robust, and how policy should ensure the ongoing protection of genetic privacy.
Personality traits are patterns of thoughts, feelings and behaviors that reflect the tendency to respond in certain ways under certain circumstances.
The Pregnancy Outcome Prediction (POP) Study is a prospective cohort study of 4,512 women who have never given birth, recruited at the Rosie Hospital between January 2008 and July 2012.
↑ Sutin DAR, Luchetti M, Aschwanden D, Stephan Y, Sesker AA, Terracciano A. (2023). "Sense of meaning and purpose in life and risk of incident dementia: New data and meta-analysis". Arch Gerontol Geriatr. 105: 104847. doi:10.1016/j.archger.2022.104847. PMID36347158.{{cite journal}}: CS1 maint: multiple names: authors list (link)
↑ Alfaro Almagro, F. (25 April 2017). "Image Processing and Quality Control for the first 10,000 Brain Imaging Datasets from UK Biobank". bioRxiv10.1101/130385.
↑ Gulcher, Jeff; Stefansson, Kari (1998). "Population Genomics: Laying the Groundwork for Genetic Disease Modeling and Targeting". Clinical Chemistry and Laboratory Medicine. 36 (8): 435–44. doi:10.1515/CCLM.1998.089. PMID9806453. S2CID6205346.
↑ An early description of the vision and business model is in Stephen D. Moore, "Biotech firm turns Iceland into a giant genetics lab," Wall Street Journal (subscription required), 3 July 1997. Another early account of the entreprise is by Michael Specter, "Decoding Iceland," The New Yorker (subscription required), 18 January 1999
↑ Anna Azvolinsky, "Master Decoder: A Profile of Kári Stefánsson," The Scientist, 1 March 2019
↑ On acquisition in 2012, its rationale in broad context, as well as deCODE being left in independent control over its data, see Matt Herper, " With DeCode deal, Amgen aims to discover drugs like we meant to in 1999," Forbes, 10 December 2012
↑ Amgen's former Chief Scientific officer, Sean Harper, in Asher Mullard, "An audience with...Sean Harper," Nature Reviews Drug Discovery (subscription required), Vol 17, pp 10-11, January 2018
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