Biology:UK Biobank

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Short description: Long-term biobank study of 500,000 people
UK Biobank
UK biobank logo.png
Biobank Stockport 1 Oct 2022.jpg
UK Biobank Co-ordinating and Assessment Centre
Mission statement"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."
Commercial?No
LocationStockport, Greater Manchester, UK
FounderRory Collins
EstablishedJanuary 2007 (2007-01)
Websitewww.ukbiobank.ac.uk

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]

Based in Stockport, Greater Manchester, it is incorporated as a limited company[6] and registered charity[7] in England and Wales, and registered as a charity[8] in Scotland.[9][10][11]

Design

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]

  • A paperless consent process
  • A touchscreen questionnaire on lifestyle and general health
  • Touchscreen tests of memory
  • An interview with a nurse on detailed medical history
  • Measurement of blood pressure
  • Measurement of sitting and standing heights
  • Measurement of weight
  • Body composition measurement using impedance
  • Measurement of grip-strength
  • Breath spirometry
  • Ultrasound bone densitometry of the heel
  • Collection of blood and urine samples

Once the visit-based assessment method was proven, the range of investigations was extended to include:[18]

  • Test of hearing discrimination
  • Measurement of arterial pulse-wave velocity
  • Measurement of visual acuity
  • Measurement of intra-ocular pressure
  • Lens refractometry
  • Fundus image of retina
  • Optical coherence tomography scan of retina
  • Electrocardiogram during exercise
  • Collection of saliva sample
  • Dietary assessment

Ethics and governance

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]

The UK Biobank Board is accountable to the members of the company (the Medical Research Council and The Wellcome Trust) and acts as company directors and as charity trustees. It is chaired by Lord Kakkar,[24] who succeeded Sir Michael Rawlins in January 2020.

Recruitment

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 100 Hz.[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]

East London Genes & Health is a genomic research study of 100,000 people of Bangladeshi and Pakistani origin carried out by Queen Mary University of London.

See also

References

  1. ↑ UK Biobank home page
  2. ↑ UK Biobank data showcase enumerating currently available data
  3. ↑ UK Biobank Ethics and Governance Council home page
  4. ↑ Will Biobank Pay Off? – 2003 BBC article mentions criticisms of UK Biobank
  5. ↑ Conroy MC, Lacey B, Bešević J, Omiyale W, Feng Q, Effingham M, Sellers J, Sheard S, Pancholi M, Gregory G, Busby J, Collins R, Allen NE. (2023). "UK Biobank: a globally important resource for cancer research". British Journal of Cancer 128: 519–527. doi:10.1038/s41416-022-02053-5. PMID 36402876. https://www.nature.com/articles/s41416-022-02053-5. 
  6. ↑ Registration number 4978912
  7. ↑ Charity Commission. UK Biobank, registered charity no. 1101332. https://apps.charitycommission.gov.uk/Showcharity/RegisterOfCharities/SearchResultHandler.aspx?RegisteredCharityNumber=1101332. 
  8. ↑ "UK Biobank, Registered Charity no. SC039230". Office of the Scottish Charity Regulator. https://www.oscr.org.uk/about-charities/search-the-register/charity-details?number=SC039230. 
  9. ↑ Sudlow, Cathie; Gallacher, John; Allen, Naomi; Beral, Valerie; Burton, Paul; Danesh, John; Downey, Paul; Elliott, Paul et al. (2015). "UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age". PLOS Medicine 12 (3): e1001779. doi:10.1371/journal.pmed.1001779. PMID 25826379. 
  10. ↑ Allen, N. E.; Sudlow, C.; Peakman, T.; Collins, R. (2014). "UK Biobank Data: Come and Get It". Science Translational Medicine 6 (224): 224ed4. doi:10.1126/scitranslmed.3008601. PMID 24553384. 
  11. ↑ Collins, Rory (2012). "What makes UK Biobank special?". The Lancet 379 (9822): 1173–1174. doi:10.1016/S0140-6736(12)60404-8. PMID 22463865. 
  12. ↑ Fry, Anna; Littlejohns, Thomas J; Sudlow, Cathie; Doherty, Nicola; Adamska, Ligia; Sprosen, Tim; Collins, Rory; Allen, Naomi E (2017-11-01). "Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population" (in en). American Journal of Epidemiology 186 (9): 1026–1034. doi:10.1093/aje/kwx246. ISSN 0002-9262. PMID 28641372. PMC 5860371. https://academic.oup.com/aje/article/186/9/1026/3883629. 
  13. ↑ 13.0 13.1 Draft protocol for the UK Biobank , 14 February 2002
  14. ↑ Reviewers' comments on Draft protocol, and responses
  15. ↑ 15.0 15.1 Andy Coghlan: One million people, one medical gamble. New Scientist, 20 January 2006
  16. ↑ Regalado, Antonio (2017-11-15). "UK Biobank supercharges medicine with gene data on 500,000 Brits" (in en). MIT Technology Review. https://www.technologyreview.com/s/609184/uk-biobank-supercharges-medicine-with-gene-data-on-500000-brits/. 
  17. ↑ 17.0 17.1 Zhang, Sarah (2017-11-06). "What Happens When You Put 500,000 People's DNA Online" (in en-US). The Atlantic. https://www.theatlantic.com/science/archive/2017/11/what-happens-when-you-put-500000-peoples-dna-online/543747/. 
  18. ↑ 18.00 18.01 18.02 18.03 18.04 18.05 18.06 18.07 18.08 18.09 18.10 18.11 18.12 18.13 18.14 18.15 18.16 18.17 Littlejohns, Thomas J.; Sudlow, Cathie; Allen, Naomi E.; Collins, Rory (2017). "UK Biobank: opportunities for cardiovascular research". European Heart Journal 40 (14): 1158–1166. doi:10.1093/eurheartj/ehx254. PMID 28531320. 
  19. ↑ 19.0 19.1 19.2 Sarah Hall: £61m medical experiment begins The Guardian , 22 August 2006
  20. ↑ UK Biobank Ethics and Governance Framework . UK Biobank, October 2007
  21. ↑ Ethics and Governance Framework for UK Biobank published for comment. Wellcome Trust, 22 September 2003
  22. ↑ Rules for UK Biobank revealed. BBC News, 24 September 2003
  23. ↑ Ethics and Governance Council formed to oversee UK Biobank Wellcome Trust, 1 November 2004
  24. ↑ "Our Board". https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/governance/our-board. 
  25. ↑ 25.0 25.1 25.2 25.3 Biobank set for national roll out. BBC News, 21 August 2006
  26. ↑ "How 500,000 Britons are critical to assessing global disease risk". Financial Times. 22 August 2018. https://www.ft.com/content/80c82a0a-a48f-11e8-8ecf-a7ae1beff35b?emailId=5b7bce24992e45000493055c. 
  27. ↑ (30 March 2012) UK biobank opens to researchers BBC News, Health, Retrieved 30 March 2015
  28. ↑ "Approved research summary" (in en-US). 2017-05-31. http://www.ukbiobank.ac.uk/approved-research/. 
  29. ↑ "Published papers, Featured Publications" (in en-US). http://www.ukbiobank.ac.uk/published-papers/. 
  30. ↑ (2015) UK Biobank; Large Scale Data Collection Axivity company web page, Retrieved 30 March 2015
  31. ↑ "AX3 3-axis logging accelerometer". 8 December 2020. https://github.com/digitalinteraction/openmovement/wiki/AX3. 
  32. ↑ Doherty, Aiden et al. (1 February 2017). "Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study". PLOS ONE 12 (2): e0169649. doi:10.1371/journal.pone.0169649. PMID 28146576. Bibcode: 2017PLoSO..1269649D. 
  33. ↑ "Showcase: Physical activity measurement". UK Biobank Data. http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=1008. 
  34. ↑ Welsh, Samantha; Peakman, Tim; Sheard, Simon; Almond, Rachael (2017-01-01). "Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort". BMC Genomics 18 (1): 26. doi:10.1186/s12864-016-3391-x. ISSN 1471-2164. PMID 28056765. 
  35. ↑ Clare, B. (2018). "The UK Biobank resource with deep phenotyping and genomic data". Nature 562 (7726): 203–209. doi:10.1038/s41586-018-0579-z. PMID 30305743. Bibcode: 2018Natur.562..203B. 
  36. ↑ Elliott, L.T. (2018). "Genome-wide association studies of brain imaging phenotypes in UK Biobank". Nature 562 (7726): 210–216. doi:10.1038/s41586-018-0571-7. PMID 30305740. Bibcode: 2018Natur.562..210E. 
  37. ↑ "UK Biobank makes available new exome sequencing data". 26 October 2020. https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-makes-available-new-exome-sequencing-data. 
  38. ↑ "UK Biobank reveals substantial variation in rates of previous COVID-19 infection across the UK". UK Biobank. 30 July 2020. https://www.ukbiobank.ac.uk/2020/07/uk-biobank-reveals-substantial-variation-in-rates-of-previous-covid-19-infection-across-the-uk/. 
  39. ↑ Ritchie, Scott C.; Surendran, Praveen; Karthikeyan, Savita; Lambert, Samuel A.; Bolton, Thomas; Pennells, Lisa; Danesh, John; Di Angelantonio, Emanuele et al. (2023). "Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants". Scientific Data 10 (1): 64. doi:10.1038/s41597-023-01949-y. Bibcode: 2023NatSD..10...64R. https://www.nature.com/articles/s41597-023-01949-y. Retrieved 12 September 2023. 
  40. ↑ Parra-Soto S, Ahumada D, Petermann-Rocha F, Boonpoor J, Gallegos JL, Anderson J, Sharp L, Malcomson FC, Livingstone KM, Mathers JC, Pell JP, Ho FK, Celis-Morales C. (2022). "Association of meat, vegetarian, pescatarian and fish-poultry diets with risk of 19 cancer sites and all cancer: findings from the UK Biobank prospective cohort study and meta-analysis". BMC Med 20 (1): 79. doi:10.1186/s12916-022-02257-9. PMID 35655214. 
  41. ↑ Anderson JJ, Darwis NDM, Mackay DF, Celis-Morales CA, Lyall DM, Sattar N, Gill JMR, Pell JP. (2018). "Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis". Eur J Cancer 90: 73–82. doi:10.1016/j.ejca.2017.11.022. PMID 29274927. https://www.sciencedirect.com/science/article/abs/pii/S0959804917314302. 
  42. ↑ Perez-Cornago A, Dunneram Y, Watts EL, Key TJ, Travis RC. (2022). "Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies". BMC Med 20 (1): 143. doi:10.1186/s12916-022-02336-x. PMID 35509091. 
  43. ↑ Hao G, Zuo L, Weng X, Fei Q, Zhang Z, Chen L, Wang Z, Jing C. (2022). "Associations of road traffic noise with cardiovascular diseases and mortality: Longitudinal results from UK Biobank and meta-analysis". Environmental Research 212 (Pt A): 113129. doi:10.1016/j.envres.2022.113129. PMID 35358546. https://www.sciencedirect.com/science/article/abs/pii/S001393512200456X. 
  44. ↑ 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. PMID 36347158. 
  45. ↑ Miller, K.L. (2016). "Multimodal population brain imaging in the UK Biobank prospective epidemiological study". Nature Neuroscience 19 (11): 1523–1536. doi:10.1038/nn.4393. PMID 27643430. 
  46. ↑ Alfaro-Almagro, F. (2016). "Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank". NeuroImage 19: 1523–1536. doi:10.1016/j.neuroimage.2017.10.034. PMID 29079522. 
  47. ↑ Alfaro Almagro, F. (25 April 2017). "Image Processing and Quality Control for the first 10,000 Brain Imaging Datasets from UK Biobank". bioRxiv 10.1101/130385.
  48. ↑ Smith SM, Douaud G, Chen W, Hanayik T, Alfaro-Almagro F, Sharp K (2021). "An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank.". Nat Neurosci 24 (5): 737–745. doi:10.1038/s41593-021-00826-4. PMID 33875891. 
  49. ↑ "Lack Of Diversity In Genetic Databases Hampers Research" (in en). https://www.npr.org/sections/health-shots/2019/08/22/752890414/lack-of-diversity-in-genetic-databases-hampers-research. 
  50. ↑ Agrawal, Raag; Prabakaran, Sudhakaran (2020-03-05). "Big data in digital healthcare: lessons learnt and recommendations for general practice". Heredity 124 (4): 525–534. doi:10.1038/s41437-020-0303-2. ISSN 0018-067X. PMID 32139886. 
  51. ↑ Daily Telegraph 2004
  52. ↑ Bingham, S.; Riboli, E. (2004). "Diet and cancer — the European Prospective Investigation into Cancer and Nutrition". Nature Reviews Cancer 4 (3): 206–15. doi:10.1038/nrc1298. PMID 14993902. http://www.angelfire.com/scary/lancelot/pdf/diet_and_cancer.pdf. 
  53. ↑ (9 February 2000) What price our genes? BBC News, Retrieved 29 January 2015
  54. ↑ Gulcher, JR; Kristjánsson, K; Gudbjartsson, H; Stefánsson, K (October 2000). "Protection of privacy by third-party encryption in genetic research in Iceland". European Journal of Human Genetics 8 (10): 739–42. doi:10.1038/sj.ejhg.5200530. PMID 11039572. 
  55. ↑ 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. PMID 9806453. 
  56. ↑ 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
  57. ↑ Anna Azvolinsky, "Master Decoder: A Profile of Kári Stefánsson," The Scientist, 1 March 2019
  58. ↑ All of the companies principal scientific discoveries are listed in chronological order on the publications page of its website
  59. ↑ 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
  60. ↑ 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
  61. ↑ Gallagher, James (26 March 2015) DNA of 'an entire nation' assessed BBC News, Health, Retrieved 29 March 2015
  62. ↑ Statistics on portal activity in: Nordic Alliance for Clinical Genomics, "NACG 6th Clinical workshop report," 21 November 2018, p.9
  63. ↑ Frank, Lane (6 October 2000). "Give and Take—Estonia's New Model for a National Gene Bank". genomenewsnetwork.org. http://www.genomenewsnetwork.org/articles/10_00/Estonias_genebank.shtml. 
  64. ↑ Frank, L. (1999). "GENETIC DISEASE:Storm Brews over Gene Bank of Estonian Population". Science 286 (5443): 1262–1263. doi:10.1126/science.286.5443.1262. PMID 10610525. 
  65. ↑ "Kui pikalt sa elad?" (in et). https://geenidoonor.ee/. 
  66. ↑ (2014) China Kadoorie Biobank University of Oxford, Retrieved 28 January 2015
  67. ↑ 67.0 67.1 "National Institutes of Health (NIH) — All of Us web page" (in en). 2018. https://allofus.nih.gov/. 
  68. ↑ Cunningham, Paige Winfield (2018-01-16). "The Health 202: NIH wants 1 million Americans to contribute to new pool of gene data" (in en-US). Washington Post. ISSN 0190-8286. https://www.washingtonpost.com/news/powerpost/paloma/the-health-202/2018/01/16/the-health-202-nih-wants-1-million-americans-to-contribute-to-new-pool-of-gene-data/5a5ba45a30fb0469e8840135/. 
  69. ↑ "All of Us Research Hub". NIH. https://www.researchallofus.org/. 
  70. ↑ Scholtens, Salome; Smidt, Nynke; Swertz, Morris A.; Bakker, Stephan JL; Dotinga, Aafje; Vonk, Judith M.; van Dijk, Freerk; Zon, Van et al. (2015-08-01). "Cohort Profile: LifeLines, a three-generation cohort study and biobank" (in en). International Journal of Epidemiology 44 (4): 1172–1180. doi:10.1093/ije/dyu229. ISSN 0300-5771. PMID 25502107. 
  71. ↑ "cohort study and biobank" (in nl-NL). https://www.lifelines.nl/researcher/biobank-lifelines. 
  72. ↑ "FinnGen, a global research project focusing on genome data of 500,000 Finns, launched" (in en). American Association for the Advancement of Science. 2017-12-19. https://www.eurekalert.org/pub_releases/2017-12/uoh-fag121917.php. 

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