China Kadoorie Biobank (CKB)

Lead Research Organisation: University of Oxford

Abstract

Chronic diseases, such as stroke, heart disease, diabetes and cancer, are the leading causes of disability and death worldwide. Understanding what causes these diseases in different populations can lead to improvements in disease prevention, risk prediction and development of new treatments. One way of identifying causes of disease is through blood-based “prospective cohort” studies, in which large numbers of apparently healthy individuals from the general population are interviewed and measured, and have blood collected and stored for future tests of genetic and non-genetic biomarkers. The health status of the study participants is then monitored “prospectively” to see who develops what disease. When sufficiently large numbers of people have developed a particular disease (“cases”), their blood and other characteristics are compared with those from “controls” who have not developed the disease. We have established one of the world’s largest studies of this kind, involving 512,000 adults in China during 2004-08. After 10-year follow-up, large numbers of disease outcomes have been accumulated, which, together with other lifestyle, environment, genetic and blood biomarker data, will enable scientists to make important discoveries about genetic and non-genetic causes of many diseases. The study findings will help improve disease prevention, prediction and treatment, benefiting populations worldwide.

Technical Summary

Despite recent advances, our ability to prevent and treat many non-communicable chronic diseases (eg, stroke, heart disease, diabetes, cancer) is still limited. Understanding what causes these diseases in diverse populations can lead to improvements in risk prediction, treatment and disease prevention, and the development of “precision” medicines. CKB is a blood-based prospective cohort study of >512,000 adults, recruited from 10 diverse areas across China (during 2004-08), with extensive data collection at baseline and subsequent resurveys and long-term storage of biological samples. By 1.1.2017, ~45,000 deaths and ~1M coded episodes of hospitalisation of ~1500 major disease types have been recorded. These exposure and outcome data are complemented by cohort-wide genotyping (currently for 102,000 participants), large-scale whole genome sequencing, and conventional and multi-omics assays for nested case-control studies of specific diseases.
Over the next 5 years, the CKB will continue to develop, maintain, and share the resource through: (i) continued follow-up for disease events through linkage to mortality/morbidity registries and health insurance systems; (ii) ascertainment, adjudication and sub-phenotyping of major disease outcomes (e.g. stroke, IHD, cancer); (iii) resurvey of ~25,000 survivors with additional enhancements (e.g. accelerometers) and new sample collection (e.g. faecal/saliva samples); (iv) maintenance, enhancement and development of IT systems underpinning the infrastructure and coordination of the study; (v) processing, managing and sharing large and complex data with the wider research community; (vi) secure bio-repositories with DNA extraction and sample reformatting.
Based on the data collected or to be generated, a wide range of research will be undertaken, both for hypothesis testing and generating. These will include (i) prospective analyses of major risk factors with major diseases and their subtypes; (ii) Genome-wide association studies of traits, lifestyle factors and diseases; (iii) Mendelian randomisation studies of causal relevance of traits for major diseases; (iv) Phenome-wide association studies of functional variants to aid drug development; (v) Comprehensive assessment of the health effects of environmental exposures (eg, ambient and household air pollution, ambient temperature, and built environment) on major CVD and non-CVD. The research priority will be given to those that are considered to be novel and to have major public health impact.
CKB is a global resource with huge potential to improve our understanding of disease aetiology, risk prediction and development of new therapies. It will also complement other large prospective studies (eg, UK Biobank) enabling investigations into a different range of genetic and other exposures that may be rare or absent in Western populations.

Publications

10 25 50

 
Description Diet, biomarkers and non-communicable diseases in rural and urban China: federated analysis of population-based studies
Amount £32,052 (GBP)
Funding ID MR/T008547/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 04/2020
 
Description Future of Animal-sourced Foods (FOAF)
Amount £4,391,572 (GBP)
Funding ID 205212/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 05/2021
 
Description Health Data Research UK Baseline Project - Oxford 6
Amount £4,000,000 (GBP)
Funding ID HDR-4006 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2018
 
Description Improving cancer prevention, risk-stratification, and detection using large-scale prospective studies in diverse populations
Amount £10,521,580 (GBP)
Funding ID C16077/A29186 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2020 
End 03/2025
 
Description The evaluation of effective healthcare delivery in China using electronic medical records for 10 years in 0.5M participants in the China Kadoorie Biobank
Amount £95,184 (GBP)
Funding ID 208126/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 10/2020
 
Description Visiting Research Fellowship Programme for the China Kadoorie Biobank
Amount £50,800 (GBP)
Organisation Sino-British Fellowship Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2017 
End 06/2022
 
Title China Kadoorie Biobank - Research Database 
Description China Kadoorie Biobank (CKB) is a blood-based prospective cohort study of 512,000 adults, recruited from 10 diverse areas across China (during 2004-08), with extensive data collection at baseline and subsequent resurveys and long-term storage of biological samples. These exposure and outcome data are complemented by separately funded genotyping (currently for 102,000 participants), whole genome sequencing, and conventional and multi-omics assays for nested case-control studies of specific diseases. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Group staff and collaborating institution have published over 300 papers using the CKB database. Since opening CKB data up for open access in September 2015, over 700 researchers have registered on the CKB Data Access System. By 18 February 2020, 352 new applications for datasets have been registered including 175 from open access users. 
URL https://www.ckbiobank.org/site/Data+Access
 
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 GWAS of miscarriage traits complete, results supplied, published in Nature Communications 2020, PMID: 33239672
Start Year 2017
 
Description Bayer - CKB Collaborative Research Programme 
Organisation Bayer
Country Germany 
Sector Private 
PI Contribution Joint initiative to: Investigation of chymase gene variants in CKB; reformat plasma samples for future multiomics assays ; conduct analyses of pilot proteomics data; perform quality control and characterisation of ~80,000 putative loss-of-function, missense, or other functionally-significant variants; develop phenome-wide and bioinformatics analyses pipelines for future work.
Collaborator Contribution Selection of variants of interest w.r.t drug targets; review of ongoing progress;
Impact Initial results for Chymase investigation in CKB; selection of CKB samples for reformatting from freezer storage initiated.
Start Year 2019
 
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 Whole Genome Sequencing of 10,000k CKB Sample underway.
Start Year 2015
 
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 NMR metabolomics GWAS complete, data supplied
Start Year 2019
 
Description Chinese Academy of Sciences: Health Effects of fatty acids and irons 
Organisation Chinese Academy of Sciences
Department Institute for Nutritional Sciences
Country China 
Sector Learned Society 
PI Contribution Established a large research project on dietary/environmental determinants and health effects of fatty acids and ions, based on CKB. This project has received major funding support from Chinese Academy of Sciences' Innovation fund to measure a whole range of fatty acid profile in erythrocyte membrane (n=10,000), ionomic profile in urine samples, as well as Hb1Ac among 25,000 resurvey participants.
Collaborator Contribution SIBS will conduct assays on samples from the China Kadoorie Biobank (CKB), including 25,000 urine and 25,000 blood red cell samples collected at the second resurvey. Red cell samples will be reformatted, and fatty acids (30 in total) assays will be conducted among the first 10,000 samples and HbA1c assays will be conducted among the total of 25,000 samples. Urine samples will be reformatted and ionomic (29 in total) and creatinine assays will be conducted.
Impact sample datasets being generated
Start Year 2016
 
Description Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes 
Organisation German Cancer Research Center
Country Germany 
Sector Academic/University 
PI Contribution Guidance and collaborative development of research project "Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes"
Collaborator Contribution Collaborative development of research project "Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes"
Impact Project funded by CRUK, Serology data generated and shared, Joint analyses ongoing.
Start Year 2017
 
Description Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes 
Organisation International Agency for Research on Cancer (IARC)
Country France 
Sector Academic/University 
PI Contribution Guidance and collaborative development of research project "Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes"
Collaborator Contribution Collaborative development of research project "Comprehensive assessment of H. pylori antigens and other infectious pathogens in the aetiology of gastric and oesophageal cancer subtypes"
Impact Project funded by CRUK, Serology data generated and shared, Joint analyses ongoing.
Start Year 2017
 
Description Developing a multiplex serology panel to detect and quantify Epstein-Barr virus infection 
Organisation German Cancer Research Center
Department Division of Chronic Inflammation and Cancer Neuenheimer Feld 242, 69120 Heidelberg
Country Germany 
Sector Academic/University 
PI Contribution Lead the development of the research proposal based on the China Kadoorie Biobank cohort. Team is proivding epidemiological, access to prospective data and samples. (Case and cohort)
Collaborator Contribution DKFZ will lead the development of a Luminex-based EBV-Monoplex panel capable of quantifying the amounts of EBV biomarkers recently be identified as best predicting nasopharyngeal carcinoma risk by proteome array.
Impact Work in progress
Start Year 2019
 
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 Metaanalysis complete, first manuscript to be submitted soon
Start Year 2017
 
Description GWAS & Sequencing Consortium of Alcohol and Nicotine 
Organisation University of Colorado
Country United States 
Sector Academic/University 
PI Contribution GWAS of smoking, alcohol, U Colorado, for the GENESCAN consortium
Collaborator Contribution GWAS results supplied. Metanalysis ongoing
Impact Summary statistics supplied, paper in preparation
Start Year 2018
 
Description McGill University 
Organisation McGill University
Department Genetic Epidemiology Richards Lab
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 Association results from up to 102K individuals for a BMD risk score with BMD and endpoints, published in Genome Medicine 2021, PMID: 33536041
Start Year 2018
 
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 Lookup of GWAS association for 118 SNPs with 20 fingerprint features provided, full GWAS provided for metaanalysis, paper in preparation
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 Association results from 31177 individuals for 247 variants supplied, revised manuscript submitted to Nature
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, USC, USA, for the SSGAC consortium
Collaborator Contribution GWAS results supplied for ~10 different traits.
Impact ~12 sets of summary stats supplied. Manuscript to be submitted soon
Start Year 2018
 
Description UCL - Lipid traits - KK 
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 Summary stats provided, data access provided to KK as visiting researcher, paper published in Nature Communications 2019, PMID: 31551420
Start Year 2019
 
Description UCL - Lipid traits - KK 
Organisation University College London
Department Division of Psychiatry
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 Summary stats provided, data access provided to KK as visiting researcher, paper published in Nature Communications 2019, PMID: 31551420
Start Year 2019
 
Description UNC School of Medicine - Psychiatric Genomes Consortium 
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 Summary stats supplied, manuscript submitted to Nature Genetics, data access provided for supplementary analyses to KK as visitiing researcher from UCL under the Psychiatric Genomes Consortium
Start Year 2018
 
Description University of Bristol 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Three projects: 1) GWAS of alcohol-related flushing and flushing 2) Within families GWAS of multiple traits 3) Mendelian randomisation of education
Collaborator Contribution Visiting researcher from Bristol working within CKB.
Impact Access to data for all three projects provided to visiting researcher. Analysese ongoing, Within families GWAS analyses completed for priority traits, manuscript submitted to Nature Genetics
Start Year 2018
 
Description University of Nottingham Malaysia/Cancer Research Malaysia 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of Risk score association results for Meta analysis
Collaborator Contribution Leadership of project and aggregations of other data sources
Impact Association results provided for 4 risk scores. Manuscript submitted to Nature Communications
Start Year 2020
 
Description Urine NMR Metabolomics 
Organisation University of Kuopio
Country Finland 
Sector Academic/University 
PI Contribution Provision of 25,000 CKB Urine samples and associated participant data for quantification of metabolites,
Collaborator Contribution Kuopio will employ a NMR-spectroscopy protocol that has been developed, optimized and validated by them to measure up to 50 biomarkers in all ~25,000 samples. Kuopio will quantify metabolite peaks and generate metabolite concentrations. Data will be available in absolute concentrations (?mol/L), as well as referenced to creatinine concentration. Data resultsin all ~25,000 samples will be shared with Oxford. As additional information for other metabolites becomes available using the NMR spectra, these will be provided to Oxford.
Impact Samples shipped, analyses being conducted
Start Year 2020
 
Description Alcohol and CVD paper engangement activities 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Media coverage of publication of alcohol and CVD, including BBC TV and radio interviews, and a press conference for national newspapers, April 2019.
Year(s) Of Engagement Activity 2019
 
Description Clinical Specialist workshop, China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact PInvited presentation at the 6th annual joint conference of Chinese Stroke Association & Tiantan International Stroke Conference 2020 (CSA&TISC 2020) - Silent Stroke in Chinese Adults: Progress and Prognosis
Year(s) Of Engagement Activity 2020
 
Description Festival of Genomics and Biodata 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on "Using human genetics to improve the odds of drug development""
Year(s) Of Engagement Activity 2021
URL https://www.festivalofgenomics.com/
 
Description Media engagement COVID-19 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Prof Chen has provided numerous interviews and opinion pieces in relation to the COVID-19 Pandemic throughout the last year. His expertise as an world leading epidemiologist and knowledge of China has been in high demand. These covered the outbreak in China and the first wave in Europe. The second wave and impact of vaccination programmes. Media channels included BBC news, Chinese and Hong Kong TV, National newspapers and Radio stations, Nature editorials.
Year(s) Of Engagement Activity 2020
 
Description Press release - overall and cause-specific death rates in China during COVID 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Series of interviews in National and international print and broadcast media following press release of a paper produced in collaboration with the Chinese Center for Disease Control and Prevention (China CDC. This examined the change in overall and cause-specific death rates during the three months of the COVID-19 outbreak in early 2020. Published in the BMJ, the report found that overall deaths did not increase in China outside Wuhan city during the first three months of the COVID-19 outbreak, with the small increase in deaths from COVID-19 more than offset by fewer deaths from other causes. Interview provided to Reuters News agency which was widely distributed.
Year(s) Of Engagement Activity 2020
 
Description Talk at Laurus Ryecroft School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact "A career as a physician scientist, pharmaceutical physician and epidemiologist"
Year(s) Of Engagement Activity 2020