The main objective of this project is to identify genes contributing to human variation in heart rate variability (HRV), a non-invasive index of cardiac parasympathetic tone and a predictor of all-cause mortality, arrhythmic events and sudden death. Eight key genes involved in biosynthesis, transport, breakdown and receptor binding of acetylcholine will be assessed by a gene-wide approach with all variants within a candidate gene considered jointly.
In this collaborative project we will use data from both the host institution (University Medical Centre Groningen, The Netherlands) and the institute from which the fellow returns (Medical College of Georgia, Augusta GA, USA). More specifically, we will use data from the TRAILS cohort (800 unrelated white youth) and data on 720 black youth drawn from the Georgia Cardiovascular Twin Study and the longitudinal BP Stress cohort. All cohorts had beat-to-beat heart rate measured at rest and during stress tasks.
We plan to calculate all the commonly used time and frequency-domain parameters of HRV by using freely available dedicated HRV software. Recent evidence suggests that the effect of genes influencing HRV at rest may be more pronounced under behavioural stress. Our study design incorporating both HRV at rest and under stress, will therefore optimize our chances of identifying genes for HRV.
The long-term objective of this project is to understand the genetic basis of cardiac autonomic function. Findings may lead to a more accurate prediction of individuals at risk, improve the effectiveness of primary interventions and contribute to individualized therapy for cardiovascular disease.
This collaborative project will allow the development of a lasting co-operation between the host institution and the scientific institute from which the fellow returns. As such it will contribute to European research and transfer knowledge acquired by the fellow while at the Medical College of Georgia in the USA.
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