Approved research

Understanding genetic influences in the response of the cardiac electrical system to exercise

Lay summary

Abnormalities in the normal electrical activity of the heart are an important cause of disease and at their most traumatic can result in sudden unexpected death. Such events can occur under stressful conditions such as exercise. We propose to study the response of a range of parameters measured from the surface electrical activity of the heart and link these with potential new genes by integrating this with the genomic information obtained in UK Biobank. Our hope is to understand the (patho)physiological response of the cardiac electrical system to exercise by combining the physiological analysis with the genomic studies. UK Biobank aims to improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses. Abnormalities of heart rhythm are a substantial health burden with stroke as a result of atrial fibrillation and sudden cardiac death in the setting of acute coronary syndromes and ischaemic heart disease being particularly common. Our study may reveal unique precipitating factors and suggest new targets for therapeutic innovation by integrating the physiological measurements with the large scale genomic characterisation. Potentially this might identify new molecular players in these responses. We would like to study the subgroup of individuals undergoing the core cardioassessment (exercise testing). Volunteers are exercised on a standing bicycle whilst a measurement is made of surface cardiac electrical activity (electrocardiogram, ECG). We would use automated computer analysis of the digitised ECGs to study how the cardiac electrical system responds to exercise. We propose a two phase study first on analysing a small number of 100 ECGs and then a much larger analysis after developing an automated algorithm. Subsequently, we will need access to data obtained in these individuals from the bespoke genotyping chip developed for UK Biobank. 100K Full cohort. Our workstream will be in two phases though (see above and below)

Scope extension:

Abnormalities in the normal electrical activity of the heart are an important cause of disease and at their most traumatic can result in sudden unexpected death. Such events can occur under stressful conditions such as exercise. We propose to study the response of a range of parameters measured from the surface electrical activity of the heart and link these with potential new genes by integrating this with the genomic information obtained in UK Biobank. Our hope is to understand the (patho)physiological response of the cardiac electrical system to exercise by combining the physiological analysis with the genomic studies.

We wish to extend the scope of our project to include validation of our genetic findings in the 500k cohort and perform genetic risk score and Mendelian randomisation analyses and also perform gene-environment analyses of ECG parameters. We also wish to test the hypothesis that decreased parasympathetic vagal tone, as measured by impaired heart rate recovery after exercise, is associated with cognitive dysfunction.

We wish to further extend the scope of our project to include cardiac imaging data in order to explore cardiac MRI measurements and their relationship to ECG parameters at rest and on exercise and risk of cardiovascular disease.

We now wish to extend the scope of our project to include pulse wave pressure waveforms (which are already part of our approved material) to explore their relationship with ECG at rest and during exercise, clinical outcomes and genomic data.