The genetics of heart rate variability

Heart rate variability (HRV) is the beat-to-beat variation over a period of time between consecutive heartbeats and is a reliable, non-invasive, economical reflection of the changes in cardiac regulation by the autonomic nervous system in response to physiological and psychological challenges. Abnormalities of autonomic activity are reflected by a reduced HRV and are strongly associated with an increased risk of cardiac events, sudden cardiac death and overall mortality. It has been shown that genetic factors are involved in HRV, but to date no genes have been found consistently. Therefore this thesis aimed at unravelling the genetic background of HRV. I first showed that 10 second electrocardiograms (ECGs) provide already valid measures for time-domain HRV traits, implying that with routinely collected ECGs sample size can be greatly improved for (genetic) epidemiological studies. In a heritability study I then demonstrated that HRV is heritable at rest and under stress, and that the genes underlying HRV in these conditions are largely the same with some genetic effects specific to the stress conditions. In a candidate gene study I explored the association of eight genes involved with acetylcholine transport or breakdown, with HRV, but no significant findings emerged. In a meta-analysis of (hypothesis-free) genome-wide association studies incorporating more than 50,000 Caucasian individuals, 11 genetic variants from eight regions were identified to be associated with HRV, many of which replicated in Hispanic/Latino and African-American individuals. Nine genes in these eight regions were found to be potentially causally related with HRV.

Dissertation: http://hdl.handle.net/11370/0fb28db2-74ef-45e1-8e61-64357047c932