UK Biobank Genetic Analyses Enhancement
Lead Research Organisation:
Wellcome Trust
Department Name: UNLISTED
Abstract
During the next 18 months, it is intended to measure about 600,000 genetic markers in the DNA extracted from blood samples that have already been collected from each of the 500,000 participants in UK Biobank. When these “genotype” measurements are combined with whole genome sequence data from a few thousand or tens of thousands of UK individuals, it will be possible to “impute” (i.e. estimate) very many more genetic variants in the region of the DNA adjacent to the variants that have been measured. The combination of these detailed genotyping data with the extensive range of known biochemical risk factors that are currently being measured in blood and urine samples from the UK Biobank participants, along with the detailed information from questionnaires and physical measurements conducted at the initial assessment visits and from linkage to health records about the development of disease during long-term follow-up, will make UK Biobank uniquely rich as a resource for researchers from all areas of health to conduct studies of the relevance of genes to disease rapidly and cost-effectively. Hence, these detailed genotype data will facilitate research that harnesses the full power of UK Biobank to help understand the causes of many different diseases.
Technical Summary
During the next 2 years, all 500,000 participants in UK Biobank will be genotyped. Dense “biobank” genotyping chips have recently been developed that combine measurement of about 250,000 SNPs in a whole-genome array, about 200,000 markers covering copy number variation, loss of function, insertions and deletions, and previously identified risk factor or disease associations, and about 150,000 exome markers which cover a high proportion of non-synonymous coding variants with allele frequency over 0.02%. These “biobank” genotyping chips provide a powerful tool for enabling genome-wide interrogation of common variants, and a scaffold that allows extension to lower frequency and rarer variants by imputation from reference sequence data sets (e.g. 1000Genomes, UK10K, GoT2D). Availability of these genotype data on the whole UK Biobank cohort would allow inference of haplotype phase at the genotyped SNPs at higher accuracy than is typical with whole-genome association studies (GWAS), using novel methods that exploit haplotype sharing within populations. The exome-focused component would allow exploration of phenotypic effects of a large number of functional coding variants, which would benefit from the data on a wide range of traits that are available on the participants in UK Biobank. Improvements in inference of phase, and the subsequent imputation, would increase the statistical power for associating genetic variants with biomarkers, phenotypes and disease outcomes. These genotyping data would remain of value even when UK Biobank participants start to be sequenced as they can be used to validate the sequencing data and to impute even more detailed genetic information for the whole cohort. Combination of such rich genotyping data with the extensive range of known biochemical risk factors currently being measured (about 50 analytes that are related to cardiovascular disease, cancer, metabolic and renal disease, and other conditions), along with the detailed phenotyping from the baseline assessment visit (which includes information about prevalent disease) and data on the development of disease during follow-up from linkage to health records, will make UK Biobank uniquely rich as a resource for scientists from all areas of health research to conduct genetic association studies rapidly and cost-effectively (since they would only need to request data rather than fund genotyping). Hence, acquisition of dense genotype data in all of the UK Biobank participants will facilitate analyses that harness the full power of the resource.
Organisations
- Wellcome Trust (Lead Research Organisation)
- AbbVie Inc (Collaboration)
- AstraZeneca (United Kingdom) (Collaboration)
- Regeneron Pharmaceuticals, Inc. (Collaboration)
- Bristol-Myers Squibb (Collaboration)
- Alnylam Pharmaceuticals (Collaboration)
- Pfizer Inc (Collaboration)
- Takeda Pharmaceutical Company (Collaboration)
- Biogen Idec (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
People |
ORCID iD |
Publications
Abraham G
(2019)
Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.
in Nature communications
Aguilar-Ramirez D
(2022)
Adiposity and NMR-measured lipid and metabolic biomarkers among 30,000 Mexican adults.
in Communications medicine
Akbari P
(2022)
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes.
in Nature communications
Alajmi K
(2017)
Abstract B16: Development of breast cancer risk prediction for the UK population using the UK Biobank dataset
in Cancer Epidemiology, Biomarkers & Prevention
Alegre-Díaz J
(2022)
Body mass index and COVID-19 mortality: prospective study of 120 000 Mexican adults.
in International journal of epidemiology
Anderson JJ
(2018)
Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis.
in European journal of cancer (Oxford, England : 1990)
Arthur RS
(2020)
Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.
in Journal of the National Cancer Institute
Au Yeung SL
(2019)
Impact of glycemic traits, type 2 diabetes and metformin use on breast and prostate cancer risk: a Mendelian randomization study.
in BMJ open diabetes research & care
Bai WY
(2020)
Identification of PIEZO1 polymorphisms for human bone mineral density.
in Bone
Batty GD
(2016)
Psychological distress, neuroticism, and cause-specific mortality: early prospective evidence from UK Biobank.
in Journal of epidemiology and community health
Beesley LJ
(2020)
The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities.
in Statistics in medicine
Beševic J
(2022)
New Horizons: the value of UK Biobank to research on endocrine and metabolic disorders.
in The Journal of clinical endocrinology and metabolism
Boutin TS
(2020)
Insights into the genetic basis of retinal detachment.
in Human molecular genetics
Buchanan CR
(2020)
The effect of network thresholding and weighting on structural brain networks in the UK Biobank.
in NeuroImage
Cai Y
(2017)
Ambient air pollution, traffic noise and adult asthma prevalence: a BioSHaRE approach.
in The European respiratory journal
Campos AI
(2020)
Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank.
in Nature communications
Carrion-Castillo A
(2020)
Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment.
in Cortex; a journal devoted to the study of the nervous system and behavior
Celis-Morales CA
(2019)
Walking Pace Is Associated with Lower Risk of All-Cause and Cause-Specific Mortality.
in Medicine and science in sports and exercise
Chan KH
(2022)
Tobacco smoking and risks of more than 470 diseases in China: a prospective cohort study.
in The Lancet. Public health
Cheesman R
(2020)
Familial Influences on Neuroticism and Education in the UK Biobank.
in Behavior genetics
Chen VL
(2020)
Genetic variants that associate with cirrhosis have pleiotropic effects on human traits.
in Liver international : official journal of the International Association for the Study of the Liver
Cheng S
(2020)
Assessing the Relationship Between Gut Microbiota and Bone Mineral Density.
in Frontiers in genetics
Description | Biobank Enhancement |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | exome sequencing of 50,000 participants |
Collaborator Contribution | creating vast amounts of genetic data to be used by researchers accessing UKBiobank |
Impact | exome data |
Start Year | 2017 |
Description | Biobank Enhancement |
Organisation | Regeneron Pharmaceuticals, Inc. |
Country | United States |
Sector | Private |
PI Contribution | exome sequencing of 50,000 participants |
Collaborator Contribution | creating vast amounts of genetic data to be used by researchers accessing UKBiobank |
Impact | exome data |
Start Year | 2017 |
Description | Genetic enhancement |
Organisation | AbbVie Inc |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Alnylam Pharmaceuticals |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Biogen Idec |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Bristol-Myers Squibb |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Pfizer Inc |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Regeneron Pharmaceuticals, Inc. |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | Genetic enhancement |
Organisation | Takeda Pharmaceutical Company |
Department | Takeda Pharmaceuticals U.S.A., Inc. (TPUSA) |
Country | United States |
Sector | Private |
PI Contribution | Partnership with Regeneron and GSK to complete exome sequencing of 450,000 UKBiobank participants |
Collaborator Contribution | The exome sequence of 50,000 UKBiobank particpants were generated through a partnership between UKB, Regeneron and GSK. Regeneron is leading a consortium of biopharma (listed) to complete exome sequencing of the remaining 450,000 participants by 2020. GSK has committed an additional £40 million investment to initiatives, such as UKB, that harness advances in genetic research in the development of new medicines. |
Impact | The first tranche of data have been incorporated back into the UKBiobank resource for the global health community to use. |
Start Year | 2018 |
Description | UK Biobank Annual Scientific Symposium |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Study participants or study members |
Results and Impact | Each year UK Biobank organises their annul scientific symposium for partcipants, scientists and funders. These events are used to inform participants about the work of the Biobank, and as a tool to encourage scientists to take part. |
Year(s) Of Engagement Activity | 2014,2015,2016,2017 |
URL | http://www.ukbiobank.ac.uk |
Description | UK Biobank Scientific Conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | The UK Biobank Scientific Symposium included presentations about the successes and future plans of the UK Biobank. It took place on 21 June 2018 in London |
Year(s) Of Engagement Activity | 2018 |
Description | UKBiobank participant events - 2014 - 2019 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Study participants or study members |
Results and Impact | UKB Biobank participants regularly attend events aimed at informing them about the work being undertaken with their data. Usually, the events last a few hours and include an overview from the chief scientist and two talks from scientists that have used UKB data. From 2014 - 2020 over 4,000 participants have taken part in events in Edinburgh (4), Manchester (4), Nottingham, Leeds, Cardiff (2), Newcastle (5), Glasgow (2), Bristol (2) and Reading(4). They are often over-subscribed and participants leave these events wishing to seek more information and support he programme in new ways (EG in imaging, genome sequencing) |
Year(s) Of Engagement Activity | 2014,2015,2016,2017,2018,2019 |
URL | http://www.ukbiobank.ac.uk |