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Background  In a recent study, we found associations of a common oxytocin receptor  (OXTR)  polymorphism with inter-individual differences in empathy, especially with emotional empathy in women. Many other studies found specific associations of oxytocin, arginine-vasopressin, serotonin and dopamine receptor gene polymorphisms with various aspects of trait empathy. As all these receptors belong to the guanine-binding protein (G protein) coupled receptor family, it is a reasonable assumption, that alterations in genes encoding G protein subunits also influence the signal transduction in empathy related circuits. However, to the best of our knowledge, these genomic variations have not yet been studied in genetic research on empathy.    Methods  Here, we analysed associations of a common polymorphism of the  GNAS  gene (C393T) in a previously characterized sample of 421 healthy blood donors (231 M, 190 F; age 18–74). The  GNAS  gene encodes the G protein adenylyl cyclase stimulator (Gαs) G protein subunit, which activates cyclic adenosine monophosphate (cAMP)-dependent pathways by stimulating the adenylyl cyclase. Cognitive and emotional aspects of dispositional empathy were tested using Davis’ Interpersonal Reactivity Index (IRI).    Results  In the complete sample, associations of C393T genotype with IRI empathy scores, including cognitive empathy (p = 0.055) and perspective taking (p = 0.057) scores did not reach a level of significance. None of the IRI scores was near to being significantly associated with C393T genotype for men alone. In females, however, genotype was significantly associated with cognitive empathy (r = -.204, p = 0.005) and perspective taking (r = -.209, p = 0.004), accounting for 4.2% and 4.4% of variability. The association of genotype with perspective taking remained significant after adjustment for multiple comparisons (p = 0.045). The 393C-allele, which had been identified as a risk factor in several medical conditions such as hypertension, obesity and diabetes, was associated with higher cognitive empathy compared to the T allele in our sample.    Conclusions  The results suggest a significant association of  GNAS  C393T genotypes with the cognitive empathic capacity of perspective taking. This association could only be found in female participants.

Sex-specific association of a common GNAS polymorphism with self-reported cognitive empathy in healthy volunteers