title: A Common Polymorphism in a Williams Syndrome Gene Predicts Amygdala Reactivity and Extraversion in Healthy Adults.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Laboratory of Neurogenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina. Electronic address: Johnna.Swartz@duke.edu.
authors: Johnna R
authors: JR
authors: Swartz
authors: Department of Psychology, University of Michigan, Ann Arbor, Michigan.
authors: Rebecca
authors: R
authors: Waller
authors: Department of Psychology, Washington University in St. Louis, St. Louis, Missouri.
authors: Ryan
authors: R
authors: Bogdan
authors: Laboratory of Neurogenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
authors: Annchen R
authors: AR
authors: Knodt
authors: Laboratory of Neurogenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
authors: Aditi
authors: A
authors: Sabhlok
authors: Department of Psychology, University of Michigan, Ann Arbor, Michigan.
authors: Luke W
authors: LW
authors: Hyde
authors: Laboratory of Neurogenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
authors: Ahmad R
authors: AR
authors: Hariri
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology*; 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 / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D019473:Transcription Factors, TFII / Q000235:genetics* / Q000502:physiology; D018980:Williams Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: C104259:GTF2I protein, human; D019473:Transcription Factors, TFII
keywords: Amygdala; Emotion; Extraversion; GTF2I; Williams syndrome; fMRI