China kadoorie biobank - University of Oxford

Lead Research Organisation: University of Oxford

Abstract

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Technical Summary

China has undergone a rapid transition in disease patterns, with chronic non-communicable diseases such as stroke, ischaemic heart disease (IHD), cancer and emphysema (COPD) accounting for most of the remaining mortality and disability. For these diseases, there are still large unexplained variations in the age specific rates between different countries and between different regions in China, indicating that important causes remain to be discovered. Heterogeneity in disease rates, non-genetic risk factors and genetic architecture, between Chinese and Western populations, and between different parts of China, helps identify new risk factors and explore known causes more comprehensively. This is particularly true for stroke, which is much less well understood in terms of genetic and non-genetic determinants than IHD.2,5,6 Stroke can be investigated particularly effectively in China, as disease rates are high and widespread use of CT/MRI allows reliable determination of stroke subtypes. Better understanding of the genetic and environmental causes of disease can lead to improvements in disease prevention, risk prediction and development of new therapies. Although retrospective case-control studies suffice for studying purely genetic factors, large bloodbased prospective studies are required for studying many non-genetic causes, and many interactions.
Genome-wide association studies (GWAS) in Caucasian have identified many disease correlates. However, some loci extend over hundreds of kilobases, involving several genes and many variants that are indistinguishable because of linkage disequilibrium (LD). Comparisons of GWAS data from the Chinese and Caucasian populations will provide opportunities to exploit local LD structure in different ethnic groups, leading to finer mapping of these known loci.
To maximise the potential of the CKB as a comprehensive and unique biomedical research resource, we wish to undertake cohort-wide genotyping, using a custom-designed 700K SNP array (Affymetrix) optimised for Chinese populations. Newton Fund support would be used exclusively for genotyping and imputation, and will allow up to 100,000 participants to be genotyped within two years. To complete genotyping of the entire CKB cohort of 0.5 million participants, additional funding will be sought from other sources in the UK and elsewhere. Because extensive baseline information and follow-up information already exists, and planned multi-omics assays of the stored biological samples is likely to be funded from other sources, information from the proposed genotyping would create a uniquely powerful and rich resource for biomedical research over the next decade or more.
 
Description BHF Centre for Research Excellence
Amount £198,595 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2016 
End 10/2018
 
Description BDI 
Organisation University of Oxford
Department Big Data Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Analyses of CKB data conducted according to group protocols and summary results supplied.
Collaborator Contribution Development of Anlaysis protocol for GWAS for miscarriage.
Impact Paper in preparation
Start Year 2017
 
Description Beijing Genomics Institute 
Organisation Beijing Genomics Institute
Country China 
Sector Academic/University 
PI Contribution In kind contributions to assay costs for various DNA projects. CKB are working with BGI on various research projects including DNA extraction and large-scale GWAS of 100,000 CKB samples. We are also collaborating with BGI's Research organisation on a Mitochondrial DNA Project. This Project involves a pilot project of high-coverage sequencing of the mitochondrial genomes of up to 100 parent-offspring trios (300 samples) from the China Kadoorie Biobank, followed by the main project of sequencing of 15,000 additional samples. These results can be used to assess the inheritance patterns of mitochondrial genomes, including the extent of heteroplasmy and paternal inheritance. Also conducting whole-genome sequencing of 10,000 samples from the China Kadoorie Biobank. The results of this project can be used to construct sequencing reference panels for imputation of genetic variants in individuals of Chinese ancestry, to assess the quality of genome-wide genotyping data, to investigate human population diversity, both within China and globally, and to identify novel genetic variants of potential relevance to human disease. Assisting with a Replication of BMI and height associations from low-coverage NGS association analyses. Framework agreements for the above projects and future research collaborations ( eg on methylation, microbiome DNA) have been agreed and are awaiting signature. Also conducting whole-genome sequencing of 10,000 samples from the China Kadoorie Biobank. The results of this project can be used to construct sequencing reference panels for imputation of genetic variants in individuals of Chinese ancestry, to assess the quality of genome-wide genotyping data, to investigate human population diversity, both within China and globally, and to identify novel genetic variants of potential relevance to human disease. Assisting with a Replication of BMI and height associations from low-coverage NGS association analyses. Framework agreements for the above projects and future research collaborations ( eg on methylation, microbiome DNA) have been agreed and being finalised
Collaborator Contribution BGI are providing the facilities and technical infrastructure for the conduct of genomic assays including data handling and shared analysis
Impact Large scale GWAS of 100,000 CKB samples complete data available for analysis. Lookup of GWAS association for ~1900 SNPs provided. Manuscript published in Cell for BMI and height GWAS
Start Year 2015
 
Description Broad Institute 
Organisation Broad Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution Sitting/standing height ratio GWAS
Collaborator Contribution Sitting/standing height ratio GWAS
Impact Analysis plan complete. Initial analyses ongoing
Start Year 2018
 
Description Cambridge Cardiology 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Metaanalysis of NMR metabolomics GWAS
Collaborator Contribution Metaanalysis of NMR metabolomics GWAS
Impact Analysis complete, data supplied
Start Year 2019
 
Description GIANT: Genetic Investigation of ANthropometric Traits 
Organisation Broad Institute
Department The Genetic Investigation of ANthropometric Traits (GIANT)
Country United States 
Sector Academic/University 
PI Contribution GWAS Data for ~28k subjects supplied to assist various meta analyses being conducted by this group. CKB involved in convening the trans-ethnic analysis sub-group.
Collaborator Contribution Large meta-analysis of Height, BMI, WHR, WHRadjBMI; Joint / consortium publications
Impact papers under preparation
Start Year 2017
 
Description GLGC 
Organisation Global Lipids Genetic Consortium (GLGC)
Country United States 
Sector Charity/Non Profit 
PI Contribution GWAS Data for ~18k subjects supplied to assist various meta analyses being conducted by this group.
Collaborator Contribution Large meta-analysis of TC, LDL-c, HDL-c, TG
Impact Papers under preparation
Start Year 2017
 
Description Imperial College London 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Signals of natural selection for lipid traits
Collaborator Contribution Signals of natural selection for lipid traits
Impact Draft analysis plan received. KK visitor within CKB, conducting analyses. Manuscript submitted.
Start Year 2019
 
Description International Stroke Genetics Consortium 
Organisation Massachusetts General Hospital
Department International Stroke Genetics Consortium
Country United States 
Sector Charity/Non Profit 
PI Contribution CKB plans to share genomics data or contribute to GWAS meta-analyses being conducted by this group. Summary statistics have been shared for GWAS of: (i) sub-arachnoid haemorrhage/ unruptured intracranial aneurysm; (ii) incident all stroke; (iii) fatal stroke, and mortality of incident stroke. Results of other analyses will only be shared after publication of CKB specific stroke genetics paper.
Collaborator Contribution Long-term collaboration. Access to additional GWAS data to increase the likelihood of novel significant findings.
Impact In Progress
Start Year 2016
 
Description McGill University 
Organisation McGill University
Country Canada 
Sector Academic/University 
PI Contribution Validation of genetic risk score for bone mineral density
Collaborator Contribution List of variants and weights supplied.
Impact Analysis ongoing
Start Year 2018
 
Description Nanjing Medical University 
Organisation Nanjing Medical University
Country China 
Sector Academic/University 
PI Contribution Access to data resulting from genotyping.
Collaborator Contribution Contributing research and analystical expertise. CKB/ Oxford hosted a post-doctoral researcher from Nanjing who is continuing to work on this project since his return.
Impact Papers currently being drafted.
Start Year 2015
 
Description Nightingale Health, Finland 
Organisation Nightingale Health Ltd.
Country Finland 
Sector Private 
PI Contribution Metaanalysis of SNPs and gene-specific GRSs with lipid/NMR data. Results sent for 13 SNPs, 3 GRSs, 228 traits, up to 17k samples.
Collaborator Contribution academic partnership
Impact Paper published in Circulation
Start Year 2018
 
Description Peking University PKU 
Organisation Peking University
Country China 
Sector Academic/University 
PI Contribution Replication of fingerprint GWAS. Lookup of GWAS association for 118 SNPs with 20 fingerprint features provided. Results of GWAS provided for metaanalysis.
Collaborator Contribution academic partnership
Impact Paper published in Circulation
Start Year 2018
 
Description Reprogen 
Organisation ReproGen Consortium
Country Global 
Sector Academic/University 
PI Contribution Conducting GWAS of reproductive traits.
Collaborator Contribution GWAS analyses complete. Currently doing lookup of existing (known) hits, and various heritability analyses. In discussion about future joint analyses/papers
Impact Joint papers
Start Year 2017
 
Description Social Science Genetics Association Consortium 
Organisation Social Science Genetics Association Consortium
Country Global 
Sector Charity/Non Profit 
PI Contribution GWAS of socioeconomic traits
Collaborator Contribution GWAS results supplied for ~10 different traits.
Impact Discussions continuing
Start Year 2018
 
Description Spirometer/BiLEVE 
Organisation University of Leicester
Department Department of Health Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Analysis in CKB of associations between spirometry measures/COPD and genetic loci identified by the Leicester group.
Collaborator Contribution Ongoing long-term collaboration.
Impact Two papers published in Nature Genetics "Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets", "New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries"
Start Year 2015
 
Description UNC School of Medicine 
Organisation University of North Carolina at Chapel Hill
Country United States 
Sector Academic/University 
PI Contribution GWAS of various psychiatric and related traits
Collaborator Contribution Analysis plan received for GWAS of Major Depression and for Depressive Symptoms. GWAS completed, summary statistics supplied.
Impact Central analysis ongoing
Start Year 2018
 
Description University of Bristol 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution GWAS of flushing
Collaborator Contribution Visiting researcher from Bristol working within CKB.
Impact Analyses ongoing
Start Year 2018
 
Description University of Cambridge - Dept of Medicine 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of controls data (300 CKB samples) for GWAS of ANCA vasculitis being conducted by Cambridge.
Collaborator Contribution The genotype data suppliedto Oxford is being used to compare the performance of the China Kadoorie Biobank and UK BioBank arrays in ethnically distinct cohorts.
Impact Joint research papers.
Start Year 2016
 
Description University of Oulu 
Organisation University of Oulu
Country Finland 
Sector Academic/University 
PI Contribution Results sent for 13 SNPs, 3 GRSs, 228 traits, up to 17k samples
Collaborator Contribution Meta-analysis of SNPs and gene-specific GRSs with lipid/NMR data. Also providing expertise on MNR metabolomics platform and analysis of CKB samples (stroke case-control study and Pancreatic cancer case-control study).
Impact paper published in Circulation: Metabolomic consequences of genetic inhibition of PCSK9 compared with statin treatment
Start Year 2017
 
Description University of Oxford - OCDEM 
Organisation University of Oxford
Department Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Access to relevant CKB data including genomics data and diabetes outcome data. Paper drafting and internal genomics expertise and supervision.
Collaborator Contribution Provision of a post graduate research assistant working on the the identification and characterization of genetic variants that influence predisposition to type 2 diabetes and related traits.
Impact Contributed several novel and interesting findings including published research papers
Start Year 2014
 
Description Wellcome Trust Centre for Human Genetics 
Organisation University of Oxford
Department Wellcome Trust Centre for Human Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Access to data resulting from genotyping.
Collaborator Contribution Collaborated in the design of a customised genotyping array for genomewide analysis, which is complementary to the UK Biobank array, and will facilitate future joint projects in the genomics of common diseases.
Impact Groups at the WTCHG work closely with the CKB team in genome wide data imputation and analysis, for work on stroke, as well as the partial cohort-wide genotyping funded by the MRC-Newton fund.
Start Year 2015
 
Description Coverage on study in Pharmaceutical industry trade journal 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Some coverage of paper on LPa2 emphasising the implications for drug target discovery and pharmaceutical inductrial practice.

https://www.drugtargetreview.com/news/12376/prospective-biobank-studies/
Year(s) Of Engagement Activity 2016
URL http://www.drugtargetreview.com/news/12376/prospective-biobank-studies/