Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups.

BACKGROUND: The specific role of the oxytocin receptor (OXTR) gene polymorphisms in emotional support seeking, related to social norms and culturally normative behavior, has been discussed in several studies. Evidence on the association between aggression and OXTR polymorphisms has also been reported. The goal of the current study was to analyze the effect of the OXTR rs53576 polymorphism, prenatal testosterone effect (second-to-fourth digit ratio, or 2D:4D), and culture on aggression assessed with the Buss-Perry Aggression Questionnaire (BPAQ). METHODS: The data were collected in Russia and Tanzania and included seven ethnic groups of European, Asian, and African origin. The total sample included 1705 adults (837 males, 868 females). All the subjects were evaluated with the BPAQ. As a measure of prenatal androgenization, the second and fourth digits were measured directly from hand, and the digit ratios were calculated. All the participants provided buccal samples, from which genomic DNA was extracted, and the OXTR gene rs53576 polymorphism was genotyped. Statistical analysis was performed using SPSS version 23.0; the alpha level for all analyses was set at 0.05. RESULTS: The ethnic group factor was the most significant predictor of ratings on BPAQ (medium effect size for physical aggression, anger and hostility scales, and low for verbal aggression). To study the effect of sex, the OXTR polymorphism, and prenatal androgenization, we conducted the z-score transformation for BPAQ scales and 2D:4D for each ethnic group and pooled these data into new z-score variables. According to the GLM analysis after leveling the effects of culture (z-transformation), all four scales of BPAQ demonstrated association with sex (main effects), with men scoring higher on physical and verbal aggression and women scoring higher on anger and hostility. Anger and hostility scales were also associated with OXTR polymorphism and 2D:4D of the right hand. The lowest levels of anger and hostility were observed in individuals with the AA genotype, especially in men. CONCLUSIONS: Our data suggest that both oxytocin (OXTR gene polymorphism) and fetal testosterone (2D:4D) may significantly affect emotional (anger) and cognitive (hostility) aggression in humans, given the leveling the role of culture.

Serotonergic gene polymorphisms (5-HTTLPR, 5HTR1A, 5HTR2A), and population differences in aggression: traditional (Hadza and Datoga) and industrial (Russians) populations compared.

BACKGROUND: Current knowledge on genetic basis of aggressive behavior is still contradictory. This may be due to the fact that the majority of studies targeting associations between candidate genes and aggression are conducted on industrial societies and mainly dealing with various types of psychopathology and disorders. Because of that, our study was carried on healthy adult individuals of both sex (n = 853). METHODS: Three populations were examined: two traditional (Hadza and Datoga) and one industrial (Russians), and the association of aggression with the following polymorphisms 5-HTTLPR, rs6295 (5HTR1A gene), and rs6311 (5HTR2A gene) were tested. Aggression was measured as total self-ratings on Buss-Perry Aggression Questionnaire. RESULTS: Distributions of allelic frequencies of 5-HTTLPR and 5HTR1A polymorphisms were significantly different among the three populations. Consequently, the association analyses for these two candidate genes were carried out separately for each population, while for the 5HTR2A polymorphism, it was conducted on the pooled data that made possible to introduce ethnic factor in the ANOVA model. The traditional biometrical approach revealed no sex differences in total aggression in all three samples. The three-way ANOVA (µ + 5-HTTLPR + 5HTR1A + 5HTR2A +ε) with measures of self-reported total aggression as dependent variable revealed significant effect of the second serotonin receptor gene polymorphism for the Hadza sample. For the Datoga, the interaction effect between 5-HTTLPR and 5HTR1A was significant. No significant effects of the used polymorphisms were obtained for Russians. The results of two-way ANOVA with ethnicity and the 5HTR2A polymorphism as main effects and their interactions revealed the highly significant effect of ethnicity, 5HTR2A polymorphism, and their interaction on total aggression. CONCLUSIONS: Our data provided obvious confirmation for the necessity to consider the population origin, as well as cultural background of tested individuals, while searching for associations between genes and behavior, and demonstrated the role of cultural attitudes towards the use of in-group aggression. Our data partly explained the reasons for disagreement in results of different teams, searching for candidate-gene associations with behavior without considerations of culturally desirable norms. Previous studies suggested that the 5HTR2A gene polymorphism associates with aggression and criminality. Our data extended these findings, demonstrating the role of rs6311 (5HTR2A gene) in aggression in adult healthy men and women from our samples. We found that G-allele carriers were rated higher on total aggression.

Polymorphisms of two loci at the oxytocin receptor gene in populations of Africa, Asia and South Europe.

BACKGROUND: The oxytocin (OT) system is known to be implicated in the regulation of complex social behavior, particularly empathy and parenting. The goal of this study was to estimate the gender and population differences in polymorphisms of two oxytocin receptor gene SNPs, rs53576 and rs2254298, in four populations. RESULTS: These data were compared with each other and with 14 samples from the corresponding regions retrieved from the 1000 Genomes database. Low level of heterozygosity was observed for both SNPs in all populations in this study (rs53576: Catalonian, Hobs = 0.413; Hadza, Hobs = 0.556; sr2254698: Khanty-Mansi, Hobs = 0.250; Datoga, Hobs = 0.550). The amount of variance due to regional variability was almost equal for both SNPs (rs53576: FRT = 0.086, rs2554298: FRT = 0.072), whereas variance for the population level of variability was twice bigger for rs2554298 (rs53576: FST = 0.127, rs2554298: FST = 0.162). Pairwise coefficients of fixation demonstrate that the Hadza were well differentiated from other African populations except of Datoga, the Datoga were weakly differentiated from other African origin populations, the Ob Ugric people were extremely differentiated from all other populations. Catalans were extremely differentiated of Asian populations. CONCLUSIONS: It is hypothesized on the base of spatial distribution of the evolutionary novel A alleles of the both OXTR gene loci, that the spread of alleles of rs22542298 and rs53376 SNPs may be associated to some extant with manipulation of parental investment in humans.