Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met polymorphism impacts novelty seeking and harm avoidance

Neuropsychopharmacology. 2010 Aug;35(9):1860-7. doi: 10.1038/npp.2010.55. Epub 2010 Apr 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain-Derived Neurotrophic Factor / genetics*
  • Epistasis, Genetic / genetics*
  • Exploratory Behavior / physiology*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genotype
  • Harm Reduction / physiology*
  • Humans
  • Male
  • Methionine / genetics*
  • Multivariate Analysis
  • Polymorphism, Genetic
  • Principal Component Analysis
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Self Concept
  • Surveys and Questionnaires
  • Valine / genetics*
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • Receptors, Dopamine D2
  • Methionine
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases
  • Valine