Yang, Albert C.Tsai, Shih-JenHong, Chen-JeeWang, CynthiaChen, Tai-JuiLiou, Ying-JayGaetano, CarloPeng, Chung-Kang2011-12-232011Yang, Albert C., Shih-Jen Tsai, Chen-Jee Hong, Cynthia Wang, Tai-Jui Chen, Ying-Jay Liou, and Chung-Kang Peng. 2011. Clustering heart rate dynamics is associated with β-adrenergic receptor polymorphisms: Analysis by information-based similarity index. PLoS ONE 6(5): e19232.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978625Background: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β -AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype–phenotype analysis to investigate the association between β -AR gene polymorphisms and heart rate dynamics. Methods: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6610.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β\(_1\)-AR Ser49Gly, β\(_2\)-AR Arg16Gly and β\(_2\)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. Results: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β\(_2\)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. Conclusions: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β\(_2\)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.en-USbiologycomputational biologymolecular geneticsgeneticshuman geneticsgenomicsphysiogenomicsmathematicsnonlinear dynamicsmedicinecardiovascularclinical geneticsneurologyelectrophysiologyautonomic nervous systemJournal Article2011-12-2310.1371/journal.pone.0019232