Cohort profile: Copenhagen Hospital Biobank - Cardiovascular Disease Cohort (CHB-CVDC): Construction of a large-scale genetic cohort to facilitate a better understanding of heart diseases

Abstract

PurposeThe 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.ParticipantsThe 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 dateHere, 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 plansIn 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.

Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

“…The Danish Data Protection Agency (P-2019-99) and the Danish National Committee on Health Research Ethics (NVK-1700704) approved the studies under which genetic data on DBDS participants were obtained. CHB is a research sample repository, which contains left-over samples obtained from diagnostic procedures on hospitalized and outpatient patients in the Danish Capital Region hospitals 47 , 48 . Genotypic data from the CHB were included as part of the study.…”

A genome-wide association study of social trust in 33,882 Danish blood donors

“…We performed a Phenome-Wide Association Study (PheWAS) to investigate the association between our two discovered lead sequence variants and a broad set of phenotypes available in the Copenhagen Hospital Biobank Cardiovascular Disease Cohort 48 (CHB-CVDC, n = 1241 International Classification of Diseases (ICD) -based Phecodes), as well as in studies including European populations stored in the GWAS Atlas resource (n = 3302 phenotypes in July 2023) 49 .…”

Multi-ancestry GWAS deciphers genetic architecture of abdominal aortic aneurysm and highlightsPCSK9as a therapeutic target

“…In addition to genetics, EHR, national socioeconomic and health registries extensively characterize each patient. Patients with AAA are included under the Copenhagen Hospital Biobank Cardiovascular Study (CHB-CVDC) (Laursen et al, 2021). The healthy blood donors from “The Danish Blood Donor Study” (DBDS) are included in the study as controls (Hansen et al, 2019).…”