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)
- 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 |
Rory Collins (Principal Investigator) |
Publications
Chua SYL
(2019)
Associations with photoreceptor thickness measures in the UK Biobank.
in Scientific reports
Stasinopoulos L
(2019)
Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study
in British Journal of Nutrition
Sarkar C
(2019)
Environmental correlates of chronic obstructive pulmonary disease in 96 779 participants from the UK Biobank: a cross-sectional, observational study.
in The Lancet. Planetary health
Dodds RM
(2020)
Sarcopenia, long-term conditions, and multimorbidity: findings from UK Biobank participants.
in Journal of cachexia, sarcopenia and muscle
Hodgson K
(2020)
Cannabis use, depression and self-harm: phenotypic and genetic relationships.
in Addiction (Abingdon, England)
Narang RK
(2020)
Do Serum Urate-associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank.
in The Journal of rheumatology
Zhao Z
(2020)
UK Biobank Whole-Exome Sequence Binary Phenome Analysis with Robust Region-Based Rare-Variant Test.
in American journal of human genetics
Campos AI
(2020)
Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank.
in Nature communications
Liu J
(2020)
The effect of liver enzymes on body composition: A Mendelian randomization study
in PLOS ONE
Ruth KS
(2020)
Using human genetics to understand the disease impacts of testosterone in men and women.
in Nature medicine
Manousaki D
(2020)
Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci.
in American journal of human genetics
Bai WY
(2020)
Identification of PIEZO1 polymorphisms for human bone mineral density.
in Bone
Cheesman R
(2020)
Familial Influences on Neuroticism and Education in the UK Biobank.
in Behavior genetics
Cheng S
(2020)
Assessing the Relationship Between Gut Microbiota and Bone Mineral Density.
in Frontiers in genetics
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)
Croall I
(2020)
Cognitive Deficit and White Matter Changes in Persons With Celiac Disease: A Population-Based Study
in Gastroenterology
Groot HE
(2020)
Genetically Determined ABO Blood Group and its Associations With Health and Disease.
in Arteriosclerosis, thrombosis, and vascular biology
Sun D
(2020)
Maternal smoking, genetic susceptibility, and birth-to-adulthood body weight.
in International journal of obesity (2005)
Mostafavi H
(2020)
Variable prediction accuracy of polygenic scores within an ancestry group.
in eLife
Trinder M
(2020)
Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease
in JAMA Cardiology
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
Cortes A
(2020)
Identifying cross-disease components of genetic risk across hospital data in the UK Biobank.
in Nature genetics
Gray JC
(2020)
Associations of cigarette smoking with gray and white matter in the UK Biobank.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Pervaiz U
(2020)
Optimising network modelling methods for fMRI.
in NeuroImage
Cirulli ET
(2020)
Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts.
in Nature communications
Maier R
(2020)
No statistical evidence for an effect of CCR5-?32 on lifespan in the UK Biobank cohort.
in Nature medicine
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
Lehto K
(2020)
Childhood Adoption and Mental Health in Adulthood: The Role of Gene-Environment Correlations and Interactions in the UK Biobank.
in Biological psychiatry
Fan M
(2020)
Sleep patterns, genetic susceptibility, and incident cardiovascular disease: a prospective study of 385 292 UK biobank participants.
in European heart journal
Hamer M
(2020)
Association between TV viewing and heart disease mortality: observational study using negative control outcome.
in Journal of epidemiology and community health
Elliott AD
(2020)
Association between physical activity and risk of incident arrhythmias in 402 406 individuals: evidence from the UK Biobank cohort.
in European heart journal
German CA
(2020)
Ordered multinomial regression for genetic association analysis of ordinal phenotypes at Biobank scale.
in Genetic epidemiology
Buchanan CR
(2020)
The effect of network thresholding and weighting on structural brain networks in the UK Biobank.
in NeuroImage
Mitani A
(2020)
Detection of anaemia from retinal fundus images via deep learning.
in Nature biomedical engineering
Wong HS
(2020)
Contribution of de novo and inherited rare CNVs to very preterm birth.
in Journal of medical 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
Pigeyre M
(2020)
ACE and Type 2 Diabetes Risk: A Mendelian Randomization Study.
in Diabetes care
Craig JE
(2020)
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
in Nature genetics
Tarroni G
(2020)
Large-scale Quality Control of Cardiac Imaging in Population Studies: Application to UK Biobank.
in Scientific reports
Welsh C
(2020)
Glycated Hemoglobin, Prediabetes, and the Links to Cardiovascular Disease: Data From UK Biobank
in Diabetes Care
Jamieson E
(2020)
Smoking, DNA Methylation, and Lung Function: a Mendelian Randomization Analysis to Investigate Causal Pathways.
in American journal of human genetics
Machado-Fragua MD
(2020)
Dairy consumption and risk of falls in 2 European cohorts of older adults.
in Clinical nutrition (Edinburgh, Scotland)
Lu T
(2020)
Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes.
in Cardiovascular diabetology
Petermann-Rocha F
(2020)
Factors associated with sarcopenia: A cross-sectional analysis using UK Biobank.
in Maturitas
Strawbridge RJ
(2020)
Carotid Intima-Media Thickness: Novel Loci, Sex-Specific Effects, and Genetic Correlations With Obesity and Glucometabolic Traits in UK Biobank.
in Arteriosclerosis, thrombosis, and vascular biology
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 |