Genome-wide association study of proneness to anger

PLoS One. 2014 Jan 28;9(1):e87257. doi: 10.1371/journal.pone.0087257. eCollection 2014.


Background: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease.

Methods: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747).

Results: Subjects were, on average, 54 (range 45-64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn.

Conclusions: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aggression
  • Anger*
  • Calcium Signaling
  • Chromosomes, Human, Pair 6
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Homeostasis
  • Hostility
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-fyn / genetics
  • Signal Transduction
  • Temperament*


  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn