UMMS Affiliation

Meyers Primary Care Institute; Department of Quantitative Health Sciences; Department of Psychiatry; Intellectual and Developmental Disabilities Research Center

Publication Date


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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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Copyright: © 2014 Mick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version



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

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PloS one

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