The applications of the IBS method in the present study were two-fold: 1) The pairwise distance of heart rate dynamics among individuals was calculated by an average of IBS distance using ntuple symbolic sequences (n = 2-10) and was used in subsequent hierarchical cluster analysis. 2) To quantify the nonlinear aspect of heart rate time series, a non-randomness index was defined to measure the symbolic patterns of heart rate dynamics away from complete randomness (i.e., absence of ordered control of the autonomic nervous system) [17] . The non-randomness index is independent of conventional entropic measures (i.e., sample entropy or approximate entropy) and has been evaluated in other studies [17, 45, 46, 47] . The calculation of the non-randomness index is based on estimating the average n-tuple distance between raw interbeat interval time series and its randomly shuffled surrogates using the IBS method, where the number of surrogates was 100 in the present study. The averaged non-randomness index derived from each n-tuple non-randomness index (n = 2-10) was then used in this study for comparisons among b-AR genotypes.