A Common Polymorphism in a Williams Syndrome Gene Predicts Amygdala Reactivity and Extraversion in Healthy Adults.
BACKGROUND
Williams syndrome (WS), a genetic disorder resulting from hemizygous microdeletion of chromosome 7q11.23, has emerged as a model for identifying the genetic architecture of socioemotional behavior. Common polymorphisms in GTF2I, which is found within the WS microdeletion, have been associated with reduced social anxiety in the general population. Identifying neural phenotypes affected by these polymorphisms would help advance our understanding not only of this specific genetic association but also of the broader neurogenetic mechanisms of variability in socioemotional behavior.


METHODS
Through an ongoing parent protocol, the Duke Neurogenetics Study, we measured threat-related amygdala reactivity to fearful and angry facial expressions using functional magnetic resonance imaging, assessed trait personality using the Revised NEO Personality Inventory, and imputed GTF2I rs13227433 from saliva-derived DNA using custom Illumina arrays. Participants included 808 non-Hispanic Caucasian, African American, and Asian university students.


RESULTS
The GTF2I rs13227433 AA genotype, previously associated with lower social anxiety, predicted decreased threat-related amygdala reactivity. An indirect effect of GTF2I genotype on the warmth facet of extraversion was mediated by decreased threat-related amygdala reactivity in women but not men.


CONCLUSIONS
A common polymorphism in the WS gene GTF2I associated with reduced social anxiety predicts decreased threat-related amygdala reactivity, which mediates an association between genotype and increased warmth in women. These results are consistent with reduced threat-related amygdala reactivity in WS and suggest that common variation in GTF2I contributes to broader variability in socioemotional brain function and behavior, with implications for understanding the neurogenetic bases of WS as well as social anxiety.
['Swartz|Johnna R|JR|', 'Waller|Rebecca|R|', 'Bogdan|Ryan|R|', 'Knodt|Annchen R|AR|', 'Sabhlok|Aditi|A|', 'Hyde|Luke W|LW|', 'Hariri|Ahmad R|AR|']
D000293:Adolescent D000328:Adult D000679:Amygdala D001931:Brain Mapping D005120:Extraversion, Psychological D005149:Facial Expression D005260:Female D007839:Functional Laterality D056726:Genetic Association Studies D005838:Genotype D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D000072861:Phobia, Social D020641:Polymorphism, Single Nucleotide D012737:Sex Factors D019473:Transcription Factors, TFII D018980:Williams Syndrome D055815:Young Adult
Williams syndrome Amygdala Extraversion GTF2I Emotion fMRI