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

Abstract

BackgroundIn 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.MethodsHere, 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).ResultsIn 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.ConclusionsThe 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.

Association between Empathy and Clinical Symptoms among Overweight and Non-Overweight Chinese Chronic Schizophrenia Patients

“…This study revealed that overweight patients exhibited higher levels of empathy compared to non-overweight patients. Although there is a paucity of literature on the empathic capacity of overweight patients, our finding is consistent with that of a previous study reporting that a metabolic-dysfunction-related gene was associated with higher cognitive empathy among female participants [47]. Moreover, another study found that among females with schizophrenia, those with higher BMI scores possessed a greater capacity for empathy [67].…”

“…Minoretti et al [78] hypothesized a possible association between the TT genotype and the schizophrenia deficiency syndrome subtype, for which affected patients typically present poor empathy [79]. However, C393C allele carriers have been shown to have more empathic tendencies, with higher IRI PT scores compared to C393T allele carriers, and the C393C allele has been recognized as a risk factor for several metabolic disorders, including obesity [47]. Third, our study observed a higher suicide rate in the overweight group, and related studies confirm that suicide relates to greater levels of empathy [80].…”

“…However, a study with inconsistent findings on the association between GNAS (guanine nucleotide binding protein, alpha stimulating) gene polymorphisms and cognitive empathy in healthy female populations reported that C393C allele carriers had higher Interpersonal Reactivity Index (IRI) perspective-taking (PT) scores in comparison to T allele carriers. Furthermore, it is noteworthy that individuals with the C393C allele have been found to have an elevated risk of metabolic disorders, including hypertension, obesity, and diabetes [47].…”

Association between self-reported empathy and level of physical activity in healthy young adults

“…Since there is a possibility that an increase in physical activity enhances neuronal plasticity in the brain regions mentioned above 16,17) , it is assumed that physical activity in healthy young adults is related to self-reported cognitive empathy. Also, there is a possibility that the genotype of the G protein coupled receptor family, including the arginine-vasopressin receptor 1a, modulates cognitive empathy 18,19) , therefore, we should investigate whether the individual differences of genotype have an influence on the relationship of physical activity with cognitive empathy or not. Although physical activity was shown to be associated with cognitive empathy, this study showed that affective empathy remained unchanged with a usual level of physical activity (Fig.…”

The sociability spectrum: evidence from reciprocal genetic copy number variations

“…Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter of complex multifaceted activity, produced in the CNS chiefly in the Raphe nuclei of the brainstem. Interestingly, multiple SNPs in the gene GNAS, encoding a G αs subunit that couples with serotonin receptors 5HT4 and 5HT7, the AVP receptor 2 and dopamine receptors of the D1-like family, have been identified in a screening of ASD patients [44][45][46][47]. Genetic association studies also linked ASD to the enzyme that catalyzes the conversion of tryptophan into 5-hydroxytryptophan (5-HTP) in the brain, tryptophan-hydroxylase 2 (TPH2) [48][49][50][51][52][53].…”