Abstract
Purpose The aim of Copenhagen Hospital Biobank-Cardiovascular Disease Cohort (CHB-CVDC) is to establish a cohort that can accelerate our understanding of CVD initiation and progression by jointly studying genetics, diagnoses, treatments and risk factors. Participants The CHB-CVDC is a large genomic cohort of patients with CVD. CHB-CVDC currently includes 96 308 patients. The cohort is part of CHB initiated in 2009 in the Capital Region of Denmark. CHB is continuously growing with ∼40 000 samples/year. Patients in CHB were included in CHB-CVDC if they were above 18 years of age and assigned at least one cardiovascular diagnosis. Additionally, up-to 110 000 blood donors can be analysed jointly with CHB-CVDC. Linkage with the Danish National Health Registries, Electronic Patient Records, and Clinical Quality Databases allow up-to 41 years of medical history. All individuals are genotyped using the Infinium Global Screening Array from Illumina and imputed using a reference panel consisting of whole-genome sequence data from 8429 Danes along with 7146 samples from North-Western Europe. Currently, 39 539 of the patients are deceased. Findings to date Here, we demonstrate the utility of the cohort by showing concordant effects between known variants and selected CVDs, that is, >93% concordance for coronary artery disease, atrial fibrillation, heart failure and cholesterol measurements and 85% concordance for hypertension. Furthermore, we evaluated multiple study designs and the validity of using Danish blood donors as part of CHB-CVDC. Lastly, CHB-CVDC has already made major contributions to studies of sick sinus syndrome and the role of phytosterols in development of atherosclerosis. Future plans In addition to genetics, electronic patient records, national socioeconomic and health registries extensively characterise each patient in CHB-CVDC and provides a promising framework for improved understanding of risk and protective variants. We aim to include other measurable biomarkers for example, proteins in CHB-CVDC making it a platform for multiomics cardiovascular studies.
| Original language | English |
|---|---|
| Article number | e049709 |
| Journal | BMJ Open |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 30 Dec 2021 |
Bibliographical note
Funding Information:myocardial infarction.1–4 Genetic studies of CAD started with linkage studies that identified monogenic causes of CAD and small candidate gene studies with dubious findings. The field has since evolved with increasing cohorts and large, international consortia such as CARDIoGRAM and CAD C4D Genetics Consortium being established.5–8 These initiatives combined with individual efforts across multiple ancestries have led to the discovery of 171 genome-wide significant CAD risk variants,9 12 HF variants10 and at least 138 atrial fibrillation (AF) loci,11 which have been replicated in independent populations. It is expected that there are many more risk variants to be discovered. Recently, biobanks such as the UK Biobank, Japan Biobank, FinnGen and the Trøndelag Health Study (The HUNT Study)12–15 have contributed to the ethnic diversity within genetic research and increased the number of both participants and phenotypes for large-scale genetic studies including studies within CVDs. Not only have numbers increased, but the detailed information captured on the individual enables a deeper phenotyping of the biobank participants with great potential to pave the way for precision cardiology. Improving our understanding of the complex interactions between genetics, lifestyle factors and individual CVDs necessitates large cohorts, such as Copenhagen Hospital Biobank (CHB)-Cardiovascular Disease Cohort (CVDC), enabling stratification of individuals into more refined and detailed phenotypes. Here, we present the CHB-CVDC, a potent resource for genetic research within CVDs. The CHB-CVDC is part of the CHB, initiated in 2009 and funded by the Department of Clinical Immunology, Copenhagen University Hospital, Denmark. The CHB takes advantage of the pre-existing blood banking system that in addition to treatment obligations (eg, blood transfusions) aims to support medical research. The data foundation of CHB is a collection of leftover EDTA blood samples from patients hospitalised in the Capital Region of Denmark, who were subject to blood typing or red blood cell antibody screening. Details about data collection, quality assessment and storage can be found in Sørensen et al.16 Presently, CHB contains samples from more than 450 000 individuals.16 Each patient is identified by a Central Person Registry (CPR) number, which facilitates linkage to nationwide registries and electronic patient records. Nationwide registries and electronic patient records are updated continuously. Patients in CHB are over 18 years old and only included once.16 The aim of the CHB-CVDC is to provide a platform for studying genetic, environmental, medical and other factors to further our knowledge of initiation, progression and manifestation of CVDs. CHB-CVDC facilitate studies of individual diseases as well as the shared risk factors, pathophysiology and disease trajectories. The ability to link CHB samples to individual data available from local hospital databases, the Danish National Health Registries, Electronic Patient Records and the Clinical Quality Databases in Denmark facilitates fine-grained stratification of patients into subpopulations. This information can be used to develop for example, risk prediction models for CAD and other CVDs.
Funding Information:
@s_brunak and Mette Nyegaard @MetteNyegaard Acknowledgements We would like to thank the patients in CHB-CVDC and the participants in DBDS. We thank deCODE genetics/Amgen and Department of Clinical Immunology, Copenhagen University Hospital for financial support of this study. Furthermore, we thank the staff working in the biobank facilities and in the hospitals whose work make the existence of this cohort sustainable. Collaborators We encourage scientific collaborations based on data generated in CHB-CVDC and summary statistics from published analyses will be made available upon request. Any collaboration needs first approval by the CHB-CVDC steering committee. Contributors IHL, KB, HH and HU conceived and planned the experiments. IHL carried out the analyses. KB, HB, SB, RF-S, HH, ES, LK, CT-P, SRO, CE, MN, HS, UT, DG, OBP, KS and HU contributed to cohort and research design. KB, DW, LT, MAHL, MS, ES, HU and SB established the data infrastructure and data governance design. HB, RF-S, ES, LK, CT-P, OBP, HS, AG, FZ, GBW, AO, GÞ, GM and HU were instrumental to data capture. IHL, KB, ADH, OP, PCH and DW contributed to analyses and interpretation of the results. IHL, KB and HU took the lead in writing the manuscript. HU is the guarantor of this work. All authors provided critical feedback, helped shape the analysis and manuscript, and approved the final version. Funding This work was supported by the Novo Nordisk Foundation (NNF) (grant numbers: NNF17OC0027594, NNF14CC0001 and NNF18SA0034956), Innovation Fund Denmark (grant number: 5153-00002B) and Nordforsk, Precision Medicine Heart (grant number: 90580 PM Heart). Competing interests The authors affiliated with deCODE genetics/Amgen are employed by the company.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Other keywords
- cardiology
- epidemiology
- genetics