Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met polymorphism impacts novelty seeking and harm avoidance.
Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N=768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D(2) receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality.
Montag
Christian
C
Department of Psychology, Laboratory of Neurogenetics, University of Bonn, Bonn, Germany. christian.montag@uni-bonn-diff.de
Markett
Sebastian
S
Basten
Ulrike
U
Stelzel
Christine
C
Fiebach
Christian
C
Canli
Turhan
T
Reuter
Martin
M
D000293:Adolescent; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D040261:Harm Reduction / Q000502:physiology*; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D025341:Principal Component Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012649:Self Concept; D011795:Surveys and Questionnaires; D014633:Valine / Q000235:genetics*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D017448:Receptors, Dopamine D2; D008715:Methionine; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D014633:Valine
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