China kadoorie biobank - University of Oxford

Lead Research Organisation: University of Oxford

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

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.

Publications


10 25 50
 
Description Beijing Genomics Institute 
Organisation Beijing Genomics Institute (BGI)
Country China, People's Republic of 
Sector Academic/University 
PI Contribution CKB are working with BGI on various research projects including DNA extravtion and large-scale GWAS of 100,000 CKB samples. We are also collaboratiing with BGI's Research organisation on a Mitochondrial DNA Project. This Project will involve 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. Framework agreement for the above project and future research collaborations ( eg on Whole genome sequencing, methylation) currently being finalised.)
Collaborator Contribution BGI are providing the facilities and technical infrastructure for the conduct of genomic assays.
Impact n/a
Start Year 2015
 
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 CKB plans to share genomics data or contribute to GWAS meta analyses being conducted by this group.
Collaborator Contribution Access to additional GWAS data to increase the likelihood of novel significant findings.
Impact N/A
Start Year 2017
 
Description Global Lipids Genetics Consortium 
Organisation Global Lipids Genetic Consortium (GLGC)
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.
Collaborator Contribution Access to additional GWAS data to increase the likelihood of novel significant findings.
Impact In progress
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.
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 Newton Fund_Cambridge 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution The ReproGen consortium is a highly active and successful international network of investigators interested in understanding the genetic basis of reproductive ageing. We use large-scale meta-analyses of Genome-wide Association Study (GWAS) data to highlight genetic variants and genes that impact reproductive timing in humans.
Collaborator Contribution joint academic collaboration
Impact n/a
Start Year 2015
 
Description Newton Fund_Oxford 
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 My research group is focused on the identification and characterization of genetic variants that influence predisposition to type 2 diabetes and related traits. We have led global efforts to extend these discovery efforts to ever larger, and more ethnicallydiverse samples. The collaboration we have established with you and your colleagues to study the genetics of diabetes in the China Kadoorie Biobank
Collaborator Contribution joint academic collaboration
Impact n/a
Start Year 2015
 
Description Newton Fund_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 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
Collaborator Contribution Ongoing long-term collaboration.
Impact Nature genetic papers (in Press) "Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets"
Start Year 2015
 
Description ROHgen - (Runs of Homozygosity) 
Organisation ReproGen Consortium
Country Global 
Sector Academic/University 
PI Contribution CKB plans to share genomics data or contribute to GWAS meta analyses being conducted by this group.
Collaborator Contribution Access to additional GWAS data to increase the likelihood of novel significant findings.
Impact In progress
Start Year 2016
 
Description University of Oxford - OCDEM 
Organisation University of Oxford
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 piblished research papers
Start Year 2014
 
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/