The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits

Acta Psychiatr Scand. 2012 Mar;125(3):194-202. doi: 10.1111/j.1600-0447.2011.01764.x. Epub 2011 Sep 8.


Objective: The aims of this study were to test the individual association of the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene (BDNF) and the GABA(A) α(6) receptor subunit gene (GABRA6) with anxiety-related traits and to explore putative gene-gene interactions in a Spanish healthy sample.

Method: A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene).

Results: Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers (F = 2.96, P = 0.019). In addition, there was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met polymorphisms (F = 3.4, P = 0.009).

Conclusion: GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene-gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety-related traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Male
  • Personality Inventory
  • Polymorphism, Genetic
  • Receptors, GABA-A / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Spain
  • Temperament*


  • Brain-Derived Neurotrophic Factor
  • GABRA6 protein, human
  • Receptors, GABA-A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins