|Title||Genome-wide association study of proneness to anger.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Mick E, McGough J, Deutsch CK, Frazier JA, Kennedy D|
|Secondary Authors||Goldberg RJ|
|Keywords||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, Signal Transduction, Temperament|
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.
|Alternate Journal||PLoS One|
|PubMed Central ID||PMC3905014|
|Grant List||R01-HL-086694 / HL / NHLBI NIH HHS / United States |
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01-HL-087641 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC- -55018 / HC / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
P30 HD004147 / HD / NICHD NIH HHS / United States
R01-HL-59367 / HL / NHLBI NIH HHS / United States
R01 MH083320 / MH / NIMH NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
P30HD004147 / HD / NICHD NIH HHS / United States
U01-HG-004402 / HG / NHGRI NIH HHS / United States