UK Biobank Genetic Analyses Enhancement

Lead Research Organisation: The Wellcome Trust Ltd

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.

Publications

10 25 50
 
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 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 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)
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 - 2019 over 3,000 participants have taken part in events in Edinburgh (2), Manchester (4), Nottingham, Leeds, Cardiff, Newcastle (4), Glasgow (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
URL http://www.ukbiobank.ac.uk