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* In 2015 and 2016, 117,500 participants completed questionnaires on occupational history and related medical information.<ref name=":0" />
* In 2015 and 2016, 117,500 participants completed questionnaires on occupational history and related medical information.<ref name=":0" />
* 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.<ref name=":0" />
* 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.<ref name=":0" />
* A genomic assay of 820,967 SNPs was conducted on the participants blood samples. Results from an initial 150,000 participants were released in 2015 and the remainder in July 2017.<ref>{{Cite journal|last=Welsh|first=Samantha|last2=Peakman|first2=Tim|last3=Sheard|first3=Simon|last4=Almond|first4=Rachael|date=2017-01-01|year=|title=Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort|url=https://dx.doi.org/10.1186/s12864-016-3391-x|journal=BMC Genomics|volume=18|pages=26|doi=10.1186/s12864-016-3391-x|issn=1471-2164|pmc=5217214|pmid=28056765|via=}}</ref><ref name=":1">{{Cite news|url=https://www.theatlantic.com/science/archive/2017/11/what-happens-when-you-put-500000-peoples-dna-online/543747/|title=What Happens When You Put 500,000 People's DNA Online|last=Zhang|first=Sarah|date=2017-11-06|work=The Atlantic|access-date=2017-11-07|language=en-US}}</ref>
* 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<ref>{{Cite journal|last=Welsh|first=Samantha|last2=Peakman|first2=Tim|last3=Sheard|first3=Simon|last4=Almond|first4=Rachael|date=2017-01-01|year=|title=Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort|url=https://dx.doi.org/10.1186/s12864-016-3391-x|journal=BMC Genomics|volume=18|pages=26|doi=10.1186/s12864-016-3391-x|issn=1471-2164|pmc=5217214|pmid=28056765|via=}}</ref><ref name=":1">{{Cite news|url=https://www.theatlantic.com/science/archive/2017/11/what-happens-when-you-put-500000-peoples-dna-online/543747/|title=What Happens When You Put 500,000 People's DNA Online|last=Zhang|first=Sarah|date=2017-11-06|work=The Atlantic|access-date=2017-11-07|language=en-US}}</ref>, and the first results in October 2018 <ref>{{Cite journal|doi=10.1038/s41586-018-0579-z |title = The UK Biobank resource with deep phenotyping and genomic data|journal = Nature|volume = 562|pages = 203–209|year = 2018|last1 = Clare|first1 = B.}}</ref><ref>{{Cite journal|doi=10.1038/s41586-018-0571-7 |title = Genome-wide association studies of brain imaging phenotypes in UK Biobank|journal = Nature|volume = 562|pages = 210–216|year = 2018|last1 = Elliott|first1 = L.T.}}</ref>.
* 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.<ref name=":0" />
* 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.<ref name=":0" />
* Data from [[National Health Service|NHS]] hospital inpatient records (England from 1996, Scotland from 1997 and Wales from 1998) were linked to the main dataset on an ongoing basis.<ref name=":0" />
* Data from [[National Health Service|NHS]] hospital inpatient records (England from 1996, Scotland from 1997 and Wales from 1998) were linked to the main dataset on an ongoing basis.<ref name=":0" />

Revision as of 07:46, 15 October 2018

UK Biobank
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]

Based in Stockport, Greater Manchester, it is incorporated as a limited company[5] and registered charity[6] in England and Wales, and registered as a charity[7] in Scotland.[8][9][10]

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.

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 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.[11][12]

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.").[13]

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.[14][15] By 2017 Biobank participants had approximately 1.3 million hospitalisations, 40,000 cancer incidents with 14,000 of them having died.[16]

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 August 22, 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.,[17] 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:[16]

Once the visit-based assessment method was proven, the range of investigations was extended to include:[16]

Ethics and governance

The UK Biobank project operates within the terms of an Ethics and Governance Framework.[18][19][20] 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.[21] The Council also advises more generally on the interests of research participants and the general public in relation to the project.

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 Prof Sir Michael Rawlins.[22]

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 enrolment was declared complete in August 2010.[23] 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.[24]

Usage

The UK Biobank dataset was opened to applications from researchers in March 2012.[25] 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.[16] By April 2017 4,600 researchers had registered to use the resource, over 880 applications had been submitted[26] and 430 research projects were completed or underway. 130 peer-reviewed articles based on the UK Biobank data had been published by January 2017.[16][27]

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.[16]
  • 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.[16]
  • 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.[28] This data was centrally processed, and listed on the Data Showcase.[29][30]
  • 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.[16]
  • In 2015 and 2016, 117,500 participants completed questionnaires on occupational history and related medical information.[16]
  • 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.[16]
  • 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[31][15], and the first results in October 2018 [32][33].
  • 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.[16]
  • 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.[16]

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[16] 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[34][35][36] and chest regions, 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.[16]
  • 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 affects.

Future plans

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.[16]
  • Linking data from NHS hospital outpatient records and GP to the main dataset were being investigated in 2018.[16]
  • Linkages to disease-specific registries and screening programs were also being investigated in 2018.[16]
  • 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".[23] Colin Blakemore, chief executive of the MRC, predicted it "will provide scientists with extraordinary information" [17] and "grow into a unique resource for future generations." [23]

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",[23] 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." [17]

The method of recruiting participants was also initially controversial. Participants were sent letters of invitation based on names, addresses, and dates of birth provided by the NHS to the UK Biobank organisers. Although compliant with UK data protection law,[37] some people objected to the NHS passing on such data to third parties without explicit consent, and also had concerns about the data security in such a large project.[citation needed]

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.[38]

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.[11][39]

In 1996 a private company deCODE genetics Inc. planned to obtain biobank samples, health and genealogical data from the whole population of Iceland - then about 270,000 people.[40] The company hoped to use the data to identify genes associated with diseases[41] and use that information to develop new drugs. deCODE genetics obtained data and DNA samples on 140,000 Icelanders[42] but filed for Chapter 11 bankruptcy in 2009[43] and as of January 2015 its systems and databanks had been spun off to another company NextCODE Health,[44] owned by WuXi PharmaTech.[45] In 2015, the Chief Executive of deCODE said that with the DNA and family tree they had data collected in Iceland, they could in theory predict which Icelandic women had a high risk of getting breast cancer. However the data had been collected anonymously.[46]

The Estonian Genome Project was started in 2000 with the aim of improving public health in the country.[47] Initially it was hoped to obtain biological samples and health data from 70% of the 1.4 million population of Estonia.[48] The project ran into financial difficulties and, as of December 2013, the project had data from 52,000 adult gene donors and the aim had been adjusted downwards to collect genealogical, genome and health data from 5% of the population.[49]

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 2004-2008 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.[50][16]

In 2006, a similar project by the U.S. National Human Genome Research Institute known as "The American project" was proposed.[13] In 2015 the US National Institutes of Health launched the "Precision Medicine Initiative" which was renamed "All of Us" in 2016.[51] This project had enrolled over 10,000 people by January 2018 in a pilot phase and aimed to sign up one million participants by 2022.[52]

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.[53][54] 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.

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.[55]

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

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. ^ Registration number 4978912
  6. ^ "UK Biobank, registered charity no. 1101332". Charity Commission for England and Wales.
  7. ^ "UK Biobank, Registered Charity no. SC039230". Office of the Scottish Charity Regulator.
  8. ^ Sudlow, Cathie; Gallacher, John; Allen, Naomi; Beral, Valerie; Burton, Paul; Danesh, John; Downey, Paul; Elliott, Paul; Green, Jane; Landray, Martin; Liu, Bette; Matthews, Paul; Ong, Giok; Pell, Jill; Silman, Alan; Young, Alan; Sprosen, Tim; Peakman, Tim; Collins, Rory (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. PMC 4380465. PMID 25826379.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ 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.
  10. ^ Collins, Rory (2012). "What makes UK Biobank special?". The Lancet. 379 (9822): 1173–1174. doi:10.1016/S0140-6736(12)60404-8. PMID 22463865.
  11. ^ a b Draft protocol for the UK Biobank Archived 2006-02-14 at the Wayback Machine, 14 February 2002
  12. ^ Reviewers' comments on Draft protocol, and responses
  13. ^ a b Andy Coghlan: One million people, one medical gamble. New Scientist, 20 January 2006
  14. ^ Regalado, Antonio (2017-11-15). "UK Biobank supercharges medicine with gene data on 500,000 Brits". MIT Technology Review. Retrieved 2018-06-25.
  15. ^ a b Zhang, Sarah (2017-11-06). "What Happens When You Put 500,000 People's DNA Online". The Atlantic. Retrieved 2017-11-07.
  16. ^ a b c d e f g h i j k l m n o p q r Littlejohns, Thomas J.; Sudlow, Cathie; Allen, Naomi E.; Collins, Rory. "UK Biobank: opportunities for cardiovascular research". European Heart Journal. doi:10.1093/eurheartj/ehx254.
  17. ^ a b c Sarah Hall: £61m medical experiment begins The Guardian, 22 August 2006
  18. ^ UK Biobank Ethics and Governance Framework Archived 2008-12-27 at the Wayback Machine. UK Biobank, October 2007
  19. ^ Ethics and Governance Framework for UK Biobank published for comment. Wellcome Trust, 22 September 2003
  20. ^ Rules for UK Biobank revealed. BBC News, 24 September 2003
  21. ^ Ethics and Governance Council formed to oversee UK Biobank Wellcome Trust, 1 November 2004
  22. ^ "UK Biobank Board". Retrieved 27 November 2014.
  23. ^ a b c d Biobank set for national roll out. BBC News, 21 August 2006
  24. ^ "How 500,000 Britons are critical to assessing global disease risk". Financial Times. 22 August 2108. Retrieved 1 October 2018. {{cite news}}: Check date values in: |date= (help)
  25. ^ (30 March 2012) UK biobank opens to researchers BBC News, Health, Retrieved 30 March 2015
  26. ^ "Approved research summary". UK Biobank. 2017-05-31. Retrieved 2017-11-08.
  27. ^ "Published papers, Featured Publications". UK Biobank. Retrieved 2017-11-08.
  28. ^ (2015) UK Biobank; Large Scale Data Collection Axivity company web page, Retrieved 30 March 2015
  29. ^ [1] Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study
  30. ^ [2] UK Biobank Data Showcase - Physical activity measurement
  31. ^ 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: 26. doi:10.1186/s12864-016-3391-x. ISSN 1471-2164. PMC 5217214. PMID 28056765.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  32. ^ Clare, B. (2018). "The UK Biobank resource with deep phenotyping and genomic data". Nature. 562: 203–209. doi:10.1038/s41586-018-0579-z.
  33. ^ Elliott, L.T. (2018). "Genome-wide association studies of brain imaging phenotypes in UK Biobank". Nature. 562: 210–216. doi:10.1038/s41586-018-0571-7.
  34. ^ Miller, K.L. (2016). "Multimodal population brain imaging in the UK Biobank prospective epidemiological study". Nature Neuroscience. 19: 1523–1536. doi:10.1038/nn.4393. PMC 5086094.
  35. ^ 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.
  36. ^ Alfaro Almagro, F. (25 April 2017). "Image Processing and Quality Control for the first 10,000 Brain Imaging Datasets from UK Biobank". bioRxiv 130385. {{cite bioRxiv}}: Check |biorxiv= value (help)
  37. ^ Why have you contacted me? Archived 2010-03-29 at the Wayback Machine
  38. ^ Daily Telegraph 2004
  39. ^ Bingham, S.; Riboli, E. (2004). "Diet and cancer — the European Prospective Investigation into Cancer and Nutrition" (PDF). Nature Reviews Cancer. 4 (3): 206–15. doi:10.1038/nrc1298. PMID 14993902.
  40. ^ (9 February 2000) What price our genes? BBC News, Retrieved 29 January 2015
  41. ^ Gudbjartsson, D. F.; Helgason, H.; Gudjonsson, S. A.; Zink, F.; Oddson, A.; Gylfason, A.; Besenbacher, S.; Magnusson, G.; Halldorsson, B. V.; Hjartarson, E.; Sigurdsson, G. T.; Stacey, S. N.; Frigge, M. L.; Holm, H.; Saemundsdottir, J.; Helgadottir, H. T.; Johannsdottir, H.; Sigfusson, G.; Thorgeirsson, G.; Sverrisson, J. T.; Gretarsdottir, S.; Walters, G. B.; Rafnar, T.; Thjodleifsson, B.; Bjornsson, E. S.; Olafsson, S.; Thorarinsdottir, H.; Steingrimsdottir, T.; Gudmundsdottir, T. S.; et al. (2015). "Large-scale whole-genome sequencing of the Icelandic population". Nature Genetics. 47 (5): 435–44. doi:10.1038/ng.3247. PMID 25807286.
  42. ^ Kaiser, Jocelyn (10 December 2012) Purchase by Amgen Won't Affect deCODE Genetics' Research, Founder Says Science, Retrieved 29 January 2015
  43. ^ MacArthur, Daniel (17 November 2009). "deCODE Genetics declare bankruptcy, will sell core business to US investors". scienceblogs.com. Archived from the original on 15 May 2012. Retrieved 29 January 2015. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  44. ^ Proffit, Allison (24 October 2013) NextCODE Health Launches deCODE's Clinical Genomics Platform Bio IT World, Retrieved 28 January 2015
  45. ^ (9 January 2015) WuXi PharmaTech Acquires NextCODE Health to Create Global Leader in Genomic Medicine PR Newswire, Retrieved 28 January 2015
  46. ^ Gallagher, James (26 March 2015) DNA of 'an entire nation' assessed BBC News, Health, Retrieved 29 March 2015
  47. ^ Frank, Lane (6 October 2000). "Give and Take—Estonia's New Model for a National Gene Bank". genomenewsnetwork.org. Retrieved 29 January 2015.
  48. ^ 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.
  49. ^ Leitsalu, L; Haller, T; Esko, T; Tammesoo, M. L.; Alavere, H; Snieder, H; Perola, M; Ng, P. C.; Mägi, R; Milani, L; Fischer, K; Metspalu, A (2014). "Cohort Profile: Estonian Biobank of the Estonian Genome Center, University of Tartu". International Journal of Epidemiology. 44 (4): 1137–47. doi:10.1093/ije/dyt268. PMID 24518929.
  50. ^ (2014) China Kadoorie Biobank University of Oxford, Retrieved 28 January 2015
  51. ^ "National Institutes of Health (NIH) — All of Us web page". US Department of Health and Human Resources - National Institutes of Health. 2018. Retrieved 2018-01-20.
  52. ^ Cunningham, Paige Winfield (2018-01-16). "The Health 202: NIH wants 1 million Americans to contribute to new pool of gene data". Washington Post. ISSN 0190-8286. Retrieved 2018-01-20.
  53. ^ Scholtens, Salome; Smidt, Nynke; Swertz, Morris A.; Bakker, Stephan JL; Dotinga, Aafje; Vonk, Judith M.; van Dijk, Freerk; Zon, Van; Kr, Sander (2015-08-01). "Cohort Profile: LifeLines, a three-generation cohort study and biobank". International Journal of Epidemiology. 44 (4): 1172–1180. doi:10.1093/ije/dyu229. ISSN 0300-5771.
  54. ^ "cohort study and biobank" (in Dutch). Retrieved 2018-05-18.
  55. ^ "FinnGen, a global research project focusing on genome data of 500,000 Finns, launched". EurekAlert!. American Association for the Advancement of Science. 2017-12-19. Retrieved 2018-02-03.
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