Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance

Abstract

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.