Mick, Eric O.McGough, James J.Deutsch, Curtis K.Frazier, Jean A.Kennedy, David NGoldberg, Robert J.2022-08-232022-08-232014-01-282014-10-03Mick 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. <a href="http://dx.doi.org/10.1371/journal.pone.0087257">Link to article on publisher's site</a>1932-6203 (Linking)10.1371/journal.pone.008725724489884https://hdl.handle.net/20.500.14038/37299BACKGROUND: 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.en-US<p>Copyright: © 2014 Mick et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>Behavioral NeurobiologyGenomicsMolecular and Cellular NeurosciencePsychiatryPsychiatry and PsychologyJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2009&amp;context=meyers_pp&amp;unstamped=1https://escholarship.umassmed.edu/meyers_pp/7116201273meyers_pp/711