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 (Collaboration)
- Alnylam Pharmaceuticals (Collaboration)
- Bristol-Myers Squibb (Collaboration)
- Regeneron Pharmaceuticals, Inc. (Collaboration)
- Pfizer Inc (Collaboration)
- Takeda Pharmaceutical Company (Collaboration)
- Biogen Idec (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
People |
ORCID iD |
Rory Collins (Principal Investigator) |
Publications
Maier R
(2020)
No statistical evidence for an effect of CCR5-?32 on lifespan in the UK Biobank cohort.
in Nature medicine
Ward J
(2019)
Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure.
in Translational psychiatry
Pervaiz U
(2020)
Optimising network modelling methods for fMRI.
in NeuroImage
German CA
(2020)
Ordered multinomial regression for genetic association analysis of ordinal phenotypes at Biobank scale.
in Genetic epidemiology
Guo W
(2015)
PL02 Body size and composition, physical activity and breast cancer risk: results from the UK biobank prospective cohort
in Journal of Epidemiology and Community Health
Johnson EC
(2021)
Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples.
in Psychological medicine
Lu T
(2020)
Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes.
in Cardiovascular diabetology
Mavaddat N
(2019)
Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.
in American journal of human genetics
Webb AJS
(2020)
Progression of Arterial Stiffness is Associated With Midlife Diastolic Blood Pressure and Transition to Late-Life Hypertensive Phenotypes.
in Journal of the American Heart Association
Yang Q
(2020)
Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health.
in International journal of epidemiology
Batty GD
(2016)
Psychological distress, neuroticism, and cause-specific mortality: early prospective evidence from UK Biobank.
in Journal of epidemiology and community health
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)
Lee MM
(2020)
Reference values for skeletal muscle mass and fat mass measured by bioelectrical impedance in 390 565 UK adults.
in Journal of cachexia, sarcopenia and muscle
Gallacher KI
(2018)
Risk factors and mortality associated with multimorbidity in people with stroke or transient ischaemic attack: a study of 8,751 UK Biobank participants.
in Journal of comorbidity
Peila R
(2020)
Risk factors for ductal carcinoma in situ of the breast in the UK Biobank cohort study.
in Cancer epidemiology
Dodds RM
(2020)
Sarcopenia, long-term conditions, and multimorbidity: findings from UK Biobank participants.
in Journal of cachexia, sarcopenia and muscle
Douaud G
(2022)
SARS-CoV-2 is associated with changes in brain structure in UK Biobank.
in Nature
Davenport S
(2020)
Selective peak inference: Unbiased estimation of raw and standardized effect size at local maxima.
in NeuroImage
Ferreira MA
(2017)
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.
in Nature genetics
Fan M
(2020)
Sleep patterns, genetic susceptibility, and incident cardiovascular disease: a prospective study of 385 292 UK biobank participants.
in European heart journal
Jamieson E
(2020)
Smoking, DNA Methylation, and Lung Function: a Mendelian Randomization Analysis to Investigate Causal Pathways.
in American journal of human genetics
Mishra A
(2022)
Stroke genetics informs drug discovery and risk prediction across ancestries.
in Nature
Cox SR
(2019)
Structural brain imaging correlates of general intelligence in UK Biobank.
in Intelligence
Kim Y
(2018)
The combination of cardiorespiratory fitness and muscle strength, and mortality risk.
in European journal of epidemiology
Verma V
(2020)
The dichotomous role of epiregulin in pain.
in Pain
Liu J
(2020)
The effect of liver enzymes on body composition: A Mendelian randomization study
in PLOS ONE
Buchanan CR
(2020)
The effect of network thresholding and weighting on structural brain networks in the UK Biobank.
in NeuroImage
Beesley L
(2019)
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
Morneau-Vaillancourt G
(2020)
The genetic and environmental hierarchical structure of anxiety and depression in the UK Biobank.
in Depression and anxiety
Pinese M
(2020)
The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly.
in Nature communications
Chan KH
(2022)
Tobacco smoking and risks of more than 470 diseases in China: a prospective cohort study.
in The Lancet. Public health
Zhao Z
(2020)
UK Biobank Whole-Exome Sequence Binary Phenome Analysis with Robust Region-Based Rare-Variant Test.
in American journal of human genetics
Conroy MC
(2023)
UK Biobank: a globally important resource for cancer research.
in British journal of cancer
Zanetti D
(2020)
Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses.
in Hypertension (Dallas, Tex. : 1979)
Ruth KS
(2020)
Using human genetics to understand the disease impacts of testosterone in men and women.
in Nature medicine
Han X
(2020)
Using Mendelian randomization to evaluate the causal relationship between serum C-reactive protein levels and age-related macular degeneration.
in European journal of epidemiology
Mostafavi H
(2020)
Variable prediction accuracy of polygenic scores within an ancestry group.
in eLife
Manousaki D
(2017)
Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study.
in PLoS medicine
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
Gale CR
(2017)
When Is Higher Neuroticism Protective Against Death? Findings From UK Biobank.
in Psychological science
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 |