Meyers Primary Care Institute; Department of Quantitative Health Sciences; Department of Psychiatry; Intellectual and Developmental Disabilities Research Center
Behavioral Neurobiology | Genomics | Molecular and Cellular Neuroscience | Psychiatry | Psychiatry and Psychology
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, lambda = 1.027 - corrected pgc = 2.2E-07, lambda = 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.
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Citation: Mick E, McGough J, Deutsch CK, Frazier JA, Kennedy D, Goldberg RJ. Genome-wide association study of proneness to anger. PLoS One. 2014 Jan 28;9(1):e87257. doi: 10.1371/journal.pone.0087257. eCollection 2014. PubMed PMID: 24489884; PubMed Central PMCID: PMC3905014. Link to article on publisher's site
Mick, Eric O.; McGough, James J.; Deutsch, Curtis K.; Frazier, Jean A.; Kennedy, David N.; and Goldberg, Robert J., "Genome-wide association study of proneness to anger" (2014). Meyers Primary Care Institute Publications and Presentations. 711.