Abstract
Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a two stage design in individuals of European descent. First, analyses were performed in a discovery sample of four cohorts (n = 3429, discovery stage). Second, findings were replicated in three independent cohorts (n = 3311, replication stage), and finally the two stages were combined in a meta-analysis (n = 6740). RMSSD data were obtained under resting conditions. After correction for multiple testing, none of the SNPs showed an association with RMSSD. In conclusion, no common genetic variants for heart rate variability were identified in the largest and most comprehensive candidate gene study on the acetylcholine pathway to date. Future gene finding efforts for RMSSD may want to focus on hypothesis free approaches such as the genome-wide association study.
Highlights
Heart rate variability (HRV) is the variation over time of the interval between consecutive heart beats
Of the 95 SNPs selected in the design stage, 87 were successfully genotyped in the Georgia cohort (GA) cohort and 90 in the TRacking Adolescents’ Individual Lives Survey (TRAILS)-P and Twin Interdisciplinary Neuroticism Study (TWINS) cohorts (Table 1)
The current study comprehensively tested the association between all common (MAF$5%) variants in eight key genes of the acetylcholine pathway and an established measure of HRV, the root mean square of successive differences (RMSSD), in subjects of European descent
Summary
Heart rate variability (HRV) is the variation over time of the interval between consecutive heart beats. HRV in the respiratory frequency range is a specific marker of parasympathetic control of the heart rhythm [1], and can be reliably assessed by the root mean square of successive differences (RMSSD) of normal RR intervals [2]. The parasympathetic (vagal) branch of the autonomic nervous system has an inhibitory influence on the pace-making activity of the sinoatrial node of the heart. Muscarinic receptors are found on all effector cells that are stimulated by the postganglionic cholinergic neurons of the parasympathetic nervous system. Nicotinic receptors are found on the postganglionic neurons of the autonomic ganglia. The two types of receptors have different functions, and specific drugs can be used to stimulate or block one or the other type [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
