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

Abstract

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.

Keywords: 2D:4D; Africans; Asians; Buss-Perry Aggression Questionnaire; Digit ratio; Ethnic groups; Europeans; Men; OXTR rs53576; Women.

Fig. 1

Distributions of the OXTR rs53576 genotypes by sex in the seven studied populations. The steady increase in proportion of GG genotypes in tested populations from east (Asia) to west (Europe and Africa)

Fig. 2

Distributions of BPAQ scales and right-hand 2D:4D for men and women from seven studied populations. R2D:4D—digit ratio of the right hand. Mean scores for BPAQ scales are presented as mean total scores per each scale. Inter-scale comparisons of raw total scores are not assumed, since each scale contains different number of questions

Fig. 3

Differences in anger and hostility (z-scores) between carriers of different OTXR rs53576 genotypes. Significant differences in anger (p = 0.016) and hostility (p = 0.018) (z-scores) are revealed by the Student’s T test between carriers of AA genotype of OXTR gene (SNP rs53576) and others (G allele carriers) in general sample (N = 1705). These differences were especially pronounced in men (N = 837), whereas within women (N = 868), differences were not statistically significant. Anger. Men: one-way ANOVA (F = 3.06, df = 2, df = 834, p = 0.047), Dunnett T3 test (AA vs. GG, p = 0.031). Women: not significant. Hostility. Men: one-way ANOVA (F = 3.68, df1 = 2, df2 = 834, p = 0.026), Dunnett T3 test (AA vs. GG, p = 0.016). Women: one-way ANOVA (F = 3.096, df = 2, df2 = 865, p = 0.046), Dunnett T3 test (not significant)

Fig. 4

Sex differences in BPAQ subscales (z-scores) (at the bottom). BPAQ scales (z-scores): PA—physical aggression, VA—verbal aggression, AN—anger, HT—hostility. Sex differences are statistically significant (Student’s T test): PA (p < 0.001), VA (p < 0.001), AN (p = 0.004), HT (p = 0.032)

Fig. 5

Partial plots for associations between anger and right-hand 2D:4D within individuals distinguished by OXTR rs53576. Regression analysis for the association between anger (z-score) and 2D:4D ratios of the right hand (R2D:4D; z-score) with control for sex: AA carriers (N = 282, beta = 0.190, t = 3.232, p = 0.001; R² _(model) = 0.051, p_(model) = 0.001); AG carriers (N = 755, beta = 0.044, t = 1.194, p = 0.233; R² _(model) = 0.011, p_(model) = 0.017); GG carriers (N = 668, beta = − 0.016, t = − 0.416, p = 0.677; R² _(model) = 0.001, p_(model) = 0.728)