Genome-wide association study of proneness to anger.
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.
Department of Quantitative Health Sciences and the Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Eric
E
Mick
Division of Child and Adolescent Psychiatry, University of California, Los Angeles Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, Los Angeles California, United States of America.
James
J
McGough
Eunice Kennedy Shriver Center, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Curtis K
CK
Deutsch
Psychiatry Department, Division of Child and Adolescent Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Jean A
JA
Frazier
Psychiatry Department, Division of Neuroinformatics and the Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
David
D
Kennedy
Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Robert J
RJ
Goldberg
D000374:Aggression; D000786:Anger; D020013:Calcium Signaling; D002896:Chromosomes, Human, Pair 6; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006706:Homeostasis; D006791:Hostility; D006801:Humans; D008297:Male; D008875:Middle Aged; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics; D015398:Signal Transduction; D013694:Temperament
C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn