Association of heart rate dynamic clusters with b-AR gene polymorphisms Next, we investigated the b-AR genotype distributions in an unsupervised cluster tree based on the dissimilarity (distance) measure of heart rate dynamics. We first estimated the pairwise distance between interbeat interval time series of all subjects using the IBS method. No violation of the triangular inequality was observed. We then applied a hierarchical clustering algorithm to cluster these subjects based on the obtained distance matrix. Two major clusters were identified in the resulting dendrogram ( Figure 2 ). There was no significant difference in age, gender, or other demographic variables between the two clusters (data not shown). Table 4 shows b-AR genotypes and standard HRV characteristics according to two major clusters. A significant deviation in the distribution of homozygous b 2 -AR Arg16 carriers was detected between the two clusters (p = 0.011), whereas the other genotypes showed no deviation in genotype distribution. In terms of standard HRV characteristics, cluster 1 (with a higher rate of homozygous b 2 -AR Arg16 carriers) showed significantly reduced LF power (p,0.001) and significantly increased HF power (p = 0.001). The clusters did not differ in other HRV indices. We verified the genotype distribution with clusters based on first-and second-half ECG data, and the results were consistent (Table S4 ).