Principal Investigator: Dr Benjamin Cairns
Institution: University of OxfordTags: 11537, Aortic stenosis, genetics, GWAS, heart disease
1a: Aortic stenosis is a narrowing of the aortic valve in the heart that affects 2-4% of older people. Aortic valve replacement is the only available option for relief of persistent symptoms, and no medicines are known to slow the progression of the disease. Discovery of genes linked to aortic stenosis could help to identify new medicines for the prevention and treatment of this disease. The aims of this study are to investigate: (i) which health and lifestyle risk factors are associated with aortic stenosis; (ii) which genetic variants increase risk of the disease; and (iii) how they do so.
1b: The objective of the proposed research is to understand the causes of aortic stenosis, which may help point the way to new medicines which can prevent or delay the progression of this disease. It therefore meets UK Biobank’s stated purpose: to “support a diverse range of research intended to improve the prevention, diagnosis and treatment of illness and the promotion of health throughout society.”
1c: This research will be conducted over several phases. Phase 1 will involve exploratory analyses and data processing. In Phase 2, we will compare individuals with and without aortic stenosis to discover genes linked to the disease. In Phase 3, we will investigate whether people with aortic stenosis differ in levels of biological markers (e.g. cholesterol), and whether such differences are related to the genes identified in Phase 2. In Phases 4 and 5, we will investigate other health and lifestyle risk factors, and risks of serious events, like heart attack, in people who have been diagnosed with aortic stenosis.
1d: The full cohort is requested for this study, both for analyses of risk factors, and to facilitate selection of participants for genetic studies. Genetic data may be required for up to the full cohort (excluding those who have not been genotyped).
UPDATED BY UK BIOBANK – 06/12/2017 PROJECT EXTENSION APPROVED:
“To extend the approved application (11537) for work on aortic stenosis (AS), we propose undertaking a descriptive, epidemiological and genetic investigation of rheumatic heart disease (RHD) in UK Biobank with particular focus on mitral stenosis (MS), a heart valve lesion that is considered to be highly specific to RHD. This extends the work described for AS, which is now primarily non-rheumatic in the UK but which earlier in the last century was predominantly a consequence of RHD. We will use genetic and phenotypic data from UK Biobank to evaluate whether the AS and MS diagnosed in recent years do indeed represent distinct disease entities, or whether they may yet share some pathophysiologic pathways.”