Additive effects of serotonergic and dopaminergic polymorphisms on trait impulsivity

Am J Med Genet B Neuropsychiatr Genet. 2012 Apr;159B(3):281-8. doi: 10.1002/ajmg.b.32025. Epub 2012 Jan 18.

Abstract

Twin studies suggest 45% heritability of trait impulsivity. Results from candidate gene studies to date are contradictory; impulsivity phenotypes were measured by different behavioral and questionnaire methods related either to the dopaminergic or to the serotonergic system. Here we report an association study of both dopaminergic (COMT rs4680, DRD4 48 bp VNTR, DRD2/ANKK1 rs1800497) and serotonergic (HTR1A rs6925, HTR1B rs13212041, SLC6A4 5-HTTLPR) gene polymorphisms and trait impulsivity assessed with the Barratt Impulsiveness Scale (BIS-11) in a sample of 687 Caucasian young adults. Results showed lower impulsivity in the presence of the DRD4 7-repeat (P = 0.006) and the HTR1B rs13212041 alleles (P = 0.003). These findings stayed significant after Bonferroni correction. A multivariate analysis using Bayesian networks confirmed independent effects of these two polymorphisms and provided a coherent characterization of the system of dependencies with respect to the impulsivity construct as well as its subscales. These results clearly suggest an additive effect of dopaminergic and serotonergic polymorphisms on trait impulsivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bayes Theorem
  • Dopamine / genetics*
  • Female
  • Gene Regulatory Networks / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • Impulsive Behavior / genetics*
  • Male
  • Multivariate Analysis
  • Polymorphism, Genetic*
  • Quantitative Trait, Heritable*
  • Receptors, Dopamine D4 / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Serotonin / genetics*
  • Young Adult

Substances

  • DRD4 protein, human
  • Receptors, Dopamine D4
  • Serotonin
  • Dopamine