AVPR1a and SLC6A4 Gene Polymorphisms Are Associated with Creative Dance Performance

Dancing, which is integrally related to music, likely has its origins close to the birth of Homo sapiens, and throughout our history, dancing has been universally practiced in all societies. We hypothesized that there are differences among individuals in aptitude, propensity, and need for dancing that may partially be based on differences in common genetic polymorphisms. Identifying such differences may lead to an understanding of the neurobiological basis of one of mankind's most universal and appealing behavioral traits—dancing. In the current study, 85 current performing dancers and their parents were genotyped for the serotonin transporter (SLC6A4: promoter region HTTLPR and intron 2 VNTR) and the arginine vasopressin receptor 1a (AVPR1a: promoter microsatellites RS1 and RS3). We also genotyped 91 competitive athletes and a group of nondancers/nonathletes (n = 872 subjects from 414 families). Dancers scored higher on the Tellegen Absorption Scale, a questionnaire that correlates positively with spirituality and altered states of consciousness, as well as the Reward Dependence factor in Cloninger's Tridimensional Personality Questionnaire, a measure of need for social contact and openness to communication. Highly significant differences in AVPR1a haplotype frequencies (RS1 and RS3), especially when conditional on both SLC6A4 polymorphisms (HTTLPR and VNTR), were observed between dancers and athletes using the UNPHASED program package (Cocaphase: likelihood ratio test [LRS] = 89.23, p = 0.000044). Similar results were obtained when dancers were compared to nondancers/nonathletes (Cocaphase: LRS = 92.76, p = 0.000024). These results were confirmed using a robust family-based test (Tdtphase: LRS = 46.64, p = 0.010). Association was also observed between Tellegen Absorption Scale scores and AVPR1a (Qtdtphase: global chi-square = 26.53, p = 0.047), SLC6A4 haplotypes (Qtdtphase: chi-square = 2.363, p = 0.018), and AVPR1a conditional on SCL6A4 (Tdtphase: LRS = 250.44, p = 0.011). Similarly, significant association was observed between Tridimensional Personality Questionnaire Reward Dependence scores and AVPR1a RS1 (chi-square = 20.16, p = 0.01). Two-locus analysis (RS1 and RS3 conditional on HTTLPR and VNTR) was highly significant (LRS = 162.95, p = 0.001). Promoter repeat regions in the AVPR1a gene have been robustly demonstrated to play a role in molding a range of social behaviors in many vertebrates and, more recently, in humans. Additionally, serotonergic neurotransmission in some human studies appears to mediate human religious and spiritual experiences. We therefore hypothesize that the association between AVPR1a and SLC6A4 reflects the social communication, courtship, and spiritual facets of the dancing phenotype rather than other aspects of this complex phenotype, such as sensorimotor integration

Correction: AVPR1a and SLC6A4 Gene Polymorphisms Are Associated with Creative Dance Performance.

[This corrects the article DOI: 10.1371/journal.pgen.0010042.]

Individual Differences in Allocation of Funds in the Dictator Game Associated with Length of the Arginine Vasopressin 1a Receptor (AVPR1a) RS3 Promoter-region and Correlation between RS3 Length and Hippocampal mRNA

Human altruism is a widespread phenomenon that puzzled evolutionary biologists since Darwin. Economic games illustrate human altruism by demonstrating that behavior deviates from economic predictions of profit maximization. A game that most plainly demonstrates this altruistic tendency is the Dictator Game. We hypothesized that human altruistic behavior is to some extent hardwired and that a likely candidate that may contribute to individual differences in altruistic behavior is the arginine vasopressin 1a (AVPR1a) receptor that in some mammals such as the vole has a profound impact on affiliative behaviors. In the current investigation, 203 male and female university students played an online version of the Dictator Game, for real money payoffs. All subjects and their parents were genotyped for AVPR1a RS1 & RS3 promoter-region repeat polymorphisms. Parents did not participate in online game playing. Since variation in the length of a repetitive element in the vole AVPR1a promoter region is associated with differences in social behavior we examined the relationship between RS1 and RS3 repeat length (base pairs) and allocation sums. Participants with short versions (308-325 bp) of the AVPR1a RS3 repeat allocated significantly (Likelihood ratio=14.75, p=0.001, DF=2) fewer shekels to the 'other' than participants with long versions (327-343 bp). We also implemented a family-based association test, UNPHASED, to confirm and validate the correlation between the AVPR1a RS3 repeat and monetary allocations in the Dictator Game. Dictator Game allocations were significantly associated with the RS3 repeat (global p value: Likelihood ratio chi-sq = 11.73, DF= 4, p-value = 0.019). The association between the AVPR1a RS3 repeat and altruism was also confirmed using two self-report scales (the Bardi-Schwartz Universalism and Benevolence Value-expressive Behavior Scales). RS3 long alleles were associated with higher scores on both measures. Finally, long AVPR1a RS3 repeats were associated with higher AVPR1a human postmortem hippocampal mRNA levels than short RS3 repeats (One way-ANOVA: F=15.04, p=0.001, DF= 14) suggesting a functional molecular genetic basis for the observation that participants with the long RS3 repeats allocate more money than participants with the short repeats. This is the first investigation showing that a common human polymorphism, with antecedents in lower mammals, contributes to decision making in an economic game. The finding that the same gene contributing to social bonding in lower animals also appears to operate similarly in human behavior suggests a common evolutionary mechanism.

Distribution of TPQ Reward Dependence Scores in Female Dancers and Nondancers/Nonathletes

<p>Distribution of TPQ Reward Dependence Scores in Female Dancers and Nondancers/Nonathletes</p

Epistatic Interaction between <i>AVPR1a</i> and <i>SLC6A4</i> Contributes to the Creative Dance Phenotype

<p>Promoter region polymorphisms in the AVPR1a receptor region possibly contribute to regional differences in brain arginine receptor 1a expression patterns [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010042#pgen-0010042-b42" target="_blank">42</a>]. Vasopressin release, and subsequent AVPR1a receptor activation, is partially regulated by serotonin (5-HT) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010042#pgen-0010042-b28" target="_blank">28</a>]. 5-HT is removed from the synapse by the serotonin transporter <i>(SLC6A4),</i> which plays a major role in regulation of synaptic levels of this neurotransmitter. In turn, synaptic <i>SLC6A4</i> mRNA and protein levels are controlled in part by the presence or absence of a promoter region 44-bp insertion/deletion [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010042#pgen-0010042-b19" target="_blank">19</a>]. Subjects with polymorphic variants of these two genes are therefore predicted to show differences in serotonergic and vasopressin tone that contribute to differences in higher psychological constructs including TPQ Reward Dependence (associated with <i>AVPR1a</i> and <i>AVPR1a</i> × <i>SLC6A4</i> gene × gene interaction) and TAS (associated with <i>SLC6A4</i> and <i>AVPR1a</i> × <i>SLC6A4</i> gene × gene interaction). Dancers score high on these two personality constructs, suggesting the hypothesis that the association between <i>AVPR1a</i> and <i>SLC6A4</i> polymorphisms and dancing is likely mediated by the action of these two genes primarily on social communication (measured by TPQ Reward Dependence scores) and spirituality (measured by TAS scores). Similar to genes contributing to other complex traits, there are no “dancing” genes but rather common polymorphisms that contribute to simpler endophenotypes [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010042#pgen-0010042-b77" target="_blank">77</a>], such as TPQ Reward Dependence and TAS, that constitute some of the critical psychological underpinnings of the dance phenotype.</p

Distribution of TAS in Female Dancers and Nondancers/Nonathletes

<p>Distribution of TAS in Female Dancers and Nondancers/Nonathletes</p