Pulse lineResearch With Heart Logo

Genome-wide association study of proneness to anger.

TitleGenome-wide association study of proneness to anger.
Publication TypeJournal Article
Year of Publication2014
AuthorsMick E, McGough J, Deutsch CK, Frazier JA, Kennedy D
Secondary AuthorsGoldberg RJ
JournalPLoS One
Volume9
Issue1
Paginatione87257
Date Published2014
ISSN1932-6203
KeywordsAggression, 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
Abstract

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.

DOI10.1371/journal.pone.0087257
Alternate JournalPLoS One
PubMed ID24489884
PubMed Central IDPMC3905014
Grant ListR01-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