The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population

Abstract

The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in (), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations.

Williams syndrome, human self-domestication, and language evolution

“…One of its functional partners is USF1 (Roy et al, 1997), whose regulatory region has undergone 30 fixed or high frequency changes after our split from Denisovans . As noted above, GTF2I has been found to affect sociality and anxiety through modulating the oxytocin reactivity (Dai et al, 2009, Brunberg et al, 2013, Procyshyn et al, 2017. Mice with a heterozygous deletion of Gtf2i tend to have a greater interest in social interactions with unfamilar mice, but reduced interest in new objects, mirroring what is observed in subjects with WS (Sakurai et al, 2011).…”

Exome sequencing of 85 Williams–Beuren syndrome cases rules out coding variation as a major contributor to remaining variance in social behavior

“…Thus, we would need a much larger sample size to investigate coding variants in GTF2I . The two linked variants in GTF2I that have previously been associated with oxytocin responsiveness and amygdala reactivity, rs1322743 and rs4717907, are intronic and were not covered in our sequencing (Procyshyn et al., ; Swartz et al., ).…”

“…However, no similar studies have investigated the social profile of WS, in spite of the fact that there is some evidence that common variation in the region can influence social behavior in the general population. For example, variation in the GTF2I gene has been associated with the WS cognitive profile, autism, oxytocin reactivity, amygdala activity, and social anxiety (Crespi & Hurd, 2014;Jabbi et al, 2015;Procyshyn, Spence, Read, Watson, & Crespi, 2017). Furthermore, genes outside of the WSCR are also likely to affect aspects of social behavior.…”

Williams syndrome

“…Recently, polymorphisms in GTF21 (general transcription factor) has been linked with high pro‐sociability, reduced social anxiety and high oxytocin levels in Williams syndrome. It is possible that GTF21 has a continuum of effects on human sociability from the extreme social phenotypes of Williams syndrome to individual differences of sociability associated with common polymorphisms in healthy populations …”

“…has a continuum of effects on human sociability from the extreme social phenotypes of Williams syndrome to individual differences of sociability associated with common polymorphisms in healthy populations. 28 The TA B L E 1 (Continued) pathologic smooth muscle cell proliferation and aortic obstruction in elastin-deficient mice. 31,32 Surgical and interventional catheter based procedures take place in one-third of patients with Williams syndrome, with 75% of those undergoing their first intervention by 5 years of age.…”