China Kadoorie Biobank (CKB) prospective study of 0.5 million adults

Lead Research Organisation: University of Oxford

Abstract

Chronic diseases, such as stroke, heart disease, 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 tested for 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. Ongoing follow-up work ensures that disease outcomes are correctly identified, checked and carefully classified before the data is analysed by researchers. We are also expanding the use of this valuable resource by the wider research community, so that many important new findings will emerge which will enable better disease prevention and treatment, benefiting populations worldwide.

Technical Summary

China Kadoorie Biobank is a blood-based prospective study of 512,000 adults, recruited during 2004-8 from 10 diverse regions of China, with extensive data collected at baseline and subsequent resurveys using questionnaires, physical measurements, and stored biological samples.
Chronic diseases are major causes of death and disability in China and worldwide. Large-scale prospective studies of multiple risk factors, with blood storage for testing novel hypotheses and detailed follow-up of health outcomes, will help assess the causes of chronic diseases. Studies in China, given the special patterns of exposures and diseases, will yield novel findings, complementing similar studies elsewhere (e.g. UK Biobank). The CKB will improve understanding of disease aetiology, risk prediction and the development of new therapies, benefitting populations worldwide.
By Q4 2016, follow-up through linkage to death and disease registries and to nationwide health insurance databases of all hospitalised events has accumulated 0.5 million hospitalised events and 35,500 deaths among CKB participants, including incident cases of stroke (42,000), IHD (35,000), cancer (23,000), diabetes (13,500) and COPD (9,500). Only ~4,000 (<1%) participants were lost to follow-up. Genome-wide data are being generated (first phase: ~100,000 participants by Q3/2016), along with blood biochemistry and multi-omics data for nested case-control studies of specific diseases.
CKB will prioritise (i) continued follow-up of cause-specific morbidity and mortality and hospital records through electronic linkage to health insurance systems; (ii) validation, clinical adjudication and detailed sub-phenotyping for selected diseases (e.g. stroke, IHD, cancer); (iii) maintenance and management of extensive and uniquely large and complex datasets; (iv) enhancement of collaboration and data sharing with the wider scientific community.
Future research based on data and samples collected to date is likely to lead to the identification of novel genetic and blood-based biomarkers involved in various chronic diseases. These can help develop improved algorithms for disease risk prediction. Biomarkers associated with early onset and/or progression of disease may also be used for early diagnosis and prediction of prognosis. Improved understanding of disease pathways and mechanisms may lead to the identification of novel therapeutic and pharmacogenetic targets that may be patentable or commercially exploitable.
Health insurance data already collected (2006-2016), includes 600,000 coded hospitalised disease events of many different types and 60 million in-hospital treatment, test and procedures-related data. Analysis of this will help evaluate the delivery of effective healthcare by quantifying over-hospitalization and inappropriate use of investigative procedures and treatments for common causes of hospitalizations.

Publications

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Du H (2016) Fruit Consumption and Cardiovascular Disease in China. in The New England journal of medicine

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Du H (2016) Fresh Fruit Consumption and Major Cardiovascular Disease in China. in The New England journal of medicine

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Guo J (2016) [Status of prevalence, awareness, treatment and controll on hypertension among adults in 10 regions, China]. in Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi

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Holmes MV (2018) Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke. in Journal of the American College of Cardiology

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Kurmi OP (2016) Validity of COPD diagnoses reported through nationwide health insurance systems in the People's Republic of China. in International journal of chronic obstructive pulmonary disease

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Lan FL (2017) [Associations between airflow obstruction and total and cause-specific mortality in adults in China]. in Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi

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Li X (2017) Tea consumption and risk of ischaemic heart disease. in Heart (British Cardiac Society)

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Liu J (2017) Prevalence of obesity among residents in Pengzhou city in Chin Modern Pre Med

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Lv J (2017) Gallstone Disease and the Risk of Type 2 Diabetes. in Scientific reports

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Lv J (2017) Adherence to Healthy Lifestyle and Cardiovascular Diseases in the Chinese Population. in Journal of the American College of Cardiology

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Meng R (2017) Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes. in International journal of epidemiology

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Meng RR (2016) [Association between famine exposure during early life and BMI in adulthood]. in Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi

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Pan DX (2016) [Interaction between smoking and indoor air pollution on chronic obstructive pulmonary diseases]. in Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi

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Pan R (2017) Cancer incidence and mortality: A cohort study in China, 2008-2013. in International journal of cancer

 
Description BHF Centre for Research Excellence
Amount £198,595 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 11/2016 
End 10/2018
 
Description CRUK Project Grant
Amount £294,057 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 11/2017 
End 10/2020
 
Description Assessing health risks associated with exposure to household and ambient air pollution in rural and urban China 
Organisation Fudan University
Department School of Public Health
Country China, People's Republic of 
Sector Academic/University 
PI Contribution Development and execution of the project "Assessing health risks associated with exposure to household and ambient air pollution in rural and urban China"
Collaborator Contribution Provision of access to additional relevant datasets on air pollution and analytical support.
Impact Field data being collected.
Start Year 2017
 
Description BDI 
Organisation University of Oxford
Department Big Data Institute
Country United Kingdom of Great Britain & Northern Ireland (UK) 
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, People's Republic of 
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 sequencing the mitochondrial genomes of up to 300 samples (up to 100 parent-offspring trios) from the China Kadoorie Biobank. 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) currently 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 submitted to Science for BMI and height GWAS
Start Year 2015
 
Description China Kadoorie Built Environment Urban Morphometric Platform 
Organisation University of Hong Kong
Country Hong Kong, Special Administrative Region of China 
Sector Academic/University 
PI Contribution Co-development of CKBUMP: China Kadoorie Built Environment Urban Morphometric Platform. To investigate a range of environmental exposures and their impact on health. CKB to provide health outcomes from Biobank participants.
Collaborator Contribution Co-development of CKBUMP: China Kadoorie Built Environment Urban Morphometric Platform. To investigate a range of environmental exposures and their impact on health. HK to provide expertise in geocoding and development of environmental exposure metrics.
Impact Work programme being developed
Start Year 2017
 
Description Chinese Academy of Sciences: Health Effects of fatty acids and irons 
Organisation Chinese Academy of Sciences
Department Institute for Nutritional Sciences
Country China, People's Republic of 
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, Federal Republic of 
Sector Public 
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
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, French Republic 
Sector Public 
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
Start Year 2017
 
Description GIANT: Genetic Investigation of ANthropometric Traits 
Organisation Broad Institute
Department The Genetic Investigation of ANthropometric Traits (GIANT)
Country United States of America 
Sector Academic/University 
PI Contribution GWAS Data for ~28k subjects supplied to assist various meta analyses being conducted by this 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 of America 
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 George Institute for Global Health 
Organisation George Institute for Global Health
Country Australia, Commonwealth of 
Sector Academic/University 
PI Contribution CKB team have provided access to data and advised on drafts of several papers considering the relationships between women's reproductive factors (such as number of pregnancies and age at menarche) and adiposity, incident cardiovascular disease and diabetes.
Collaborator Contribution Two George Institute staff have dedicated significant time to analysis of results and drafting of papers
Impact Five review papers have been published to date.
Start Year 2015
 
Description Imperial College London 
Organisation Imperial College London
Department Department of Epidemiology and Biostatistics
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Provision of relevant baseline from CKB to contribute to the Non-Communicable Disease (NCD) Risk Factor Collaboration funded by the Wellcome Trust.
Collaborator Contribution Providing estimates of country/regional trends in major cardio-metabolic risk factors for non-communicable diseases (NCDs), globally; these include body mass index, cholesterol, blood pressure and glucose.
Impact Papers under preparation
Start Year 2017
 
Description International Stroke Genetics Consortium 
Organisation Massachusetts General Hospital
Department International Stroke Genetics Consortium
Country United States of America 
Sector Charity/Non Profit 
PI Contribution CKB plans to share genomics data or contribute to GWAS meta-analyses being conducted by this group. Sharing to take please 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 Lund University: Pancreatic Cancer 
Organisation Lund University
Department Department of Immunotechnology
Country Sweden, Kingdom of 
Sector Hospitals 
PI Contribution Access to CKB samples as part of a case control study. Including details metabolomic and proteomic profiling.
Collaborator Contribution Proteomic Assays, joint analysis of results.
Impact Potential joint research papers on early diagnosis methods for pancreatic cancer.
Start Year 2016
 
Description Nanjing Medical University 
Organisation Nanjing Medical University
Country China, People's Republic of 
Sector Academic/University 
PI Contribution Access to data resulting from genotyping.
Collaborator Contribution Contributing research and analystical expertise. CKB/ Oxford currently hosting a post-doctoral researcher from Nanjing who is working on this project.
Impact Papers currentry being drafted.
Start Year 2015
 
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 Short-and long-term effects of outdoor pollution 
Organisation Chinese University of Hong Kong
Country Hong Kong, Special Administrative Region of China 
Sector Academic/University 
PI Contribution Development of a programme of collaborative research to examine both short- and long- term effects of outdoor air pollution (together with climate model and geocoding) on health outcomes. Individual socio-demographic factors, as well as climate-related factors and indoor air pollutants would also be examined as independent and interacting factors which contribute to health outcomes.
Collaborator Contribution Development of a programme of collaborative research to examine both short- and long- term effects of outdoor air pollution (together with climate model and geocoding) on health outcomes. Individual socio-demographic factors, as well as climate-related factors and indoor air pollutants would also be examined as independent and interacting factors which contribute to health outcomes.
Impact Development of project: Assessing health risks associated with exposure to household and ambient air pollution in rural and urban China
Start Year 2017
 
Description UK BiLEVE 
Organisation UK Biobank
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Charity/Non Profit 
PI Contribution GWAS Data for ~33k subjects supplied to assist various meta analyses being conducted by this group.
Collaborator Contribution Consortium is investigating SNP and GRS associations with COPD and COPD exacerbations.
Impact One peer-reviewed paper published, others under preparation
Start Year 2017
 
Description University of Cambridge 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Multiple 
PI Contribution Provision of relevant baseline and follow-up data from CKB and guidance on anlaysis plans and interpretation of results.
Collaborator Contribution Cambridge will conduct an analysis of the associations between fish and soya bean intake and incidence of type 2 diabetes: an individual participant meta-analysis.
Impact papers under preparation
Start Year 2017
 
Description University of Cambridge - Dept of Medicine 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
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 Edinburgh 
Organisation University of Edinburgh
Department Centre for Population Health Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Provision of relevant baseline and follow-up data from CKB and guidance on analysis plans and interpretation of results.
Collaborator Contribution Edinburgh will investigate and describe the association between socioeconomic status and prevalent and incident diabetes in China with investigation of the role of mediating and confounding factors.
Impact Papers under preparation
Start Year 2017
 
Description University of Leicester 
Organisation University of Leicester
Department Department of Health Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Access to data resulting from genotyping, joint analyses
Collaborator Contribution CKB has included additional custom respiratory content into its array design and Prof Tobin will assist in examining this GWAs data alongside baseline and prospective datasets
Impact Nature genetics paper. Nat Genet 2017; 49(3):416-425. More under preparation
Start Year 2015
 
Description University of Oulu 
Organisation University of Oulu
Country Finland, Republic of 
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 under preparation
Start Year 2017
 
Description University of Oxford - OCDEM 
Organisation University of Oxford
Department Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
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 Already contributed several novel and interesting findings including published research papers
Start Year 2014
 
Description University of Oxford Biomedical Engineering 
Organisation University of Oxford
Department Mathematical, Physical & Life Sciences Division
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Access to ECG wave data from CKB resurvey. Joint analyses.
Collaborator Contribution the development of machine learning methods for modelling ECG time series data within the CKB, and where we plan to develop tools for automatically fusing ECG-based data into disease sub-phenotyping for the CKB cohort. Also keen to explore other aspects of the CKB data resource, including genotypical biomarker data.
Impact One research paper published
Start Year 2014
 
Description Wellcome Trust Centre for Human Genetics 
Organisation University of Oxford
Department Wellcome Trust Centre for Human Genetics
Country United Kingdom of Great Britain & Northern Ireland (UK) 
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 PE talk for CRUK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact one public engagement talk at a fundraiser in aid of CRUK. It was on the 28th Oct 2017
Year(s) Of Engagement Activity 2017
 
Description PE talk for CRUK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact CRUK Public Engagement on March 14th (next Wednesday), and about 200 senior school students will attend. I will show them a model of prospective study of associations between air pollution, smoking and fruit/vegetable intake with risk of lung cancer. Being held in the RDB
Year(s) Of Engagement Activity 2018