Effect of tryptophan hydroxylase-2 gene polymorphism G-703 T on personality in a population representative sample

Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3:57:31-5. doi: 10.1016/j.pnpbp.2014.10.005. Epub 2014 Oct 22.


The tryptophan hydroxylase-2 gene (TPH2) is coding for the key enzyme of serotonin (5-HT) synthesis in the brain and has been associated with a number of psychiatric conditions. A functional variation in the TPH2 gene (G-703T, rs4570625) has been found to affect anxiety-related personality; however, information is very limited regarding the five factor model (FFM) personality traits. We have examined the association of the TPH2 G-703T polymorphism with FFM personality traits, and the possible modulation by the functional variation in the serotonin transporter gene (5-HTTLPR) in a large longitudinal population representative sample. The FFM personality traits were assessed in both birth cohorts of the Estonian Children Personality Behaviour and Health Study at ages 15 (n=742) and 18 (n=834). Significant association of the TPH2 genotype with Neuroticism and Conscientiousness was found at age 15, and with Extraversion and Conscientiousness at age 18. Participants with the T/T genotype scored significantly lower on Neuroticism and higher on Conscientiousness and Extraversion scales. In addition, a gene×gene interaction effect on Conscientiousness was revealed: the TPH2 genotype effect was evident only in the 5-HTTLPR S-allele carriers. These results provide further evidence on the possible role of genetic variations in 5-HT neurotransmission on development of personality traits, and suggest a functional interaction between two key proteins in the 5-HT-ergic system.

Keywords: 5-HTTLPR; Epistasis; Gene×gene interaction; Personality; TPH2 G-703T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aging / genetics
  • Aging / psychology*
  • Anxiety Disorders / genetics
  • Epistasis, Genetic / genetics
  • Extraversion, Psychological
  • Female
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Neuroticism
  • Personality / genetics*
  • Personality Assessment
  • Polymorphism, Single Nucleotide / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Tryptophan Hydroxylase / genetics*
  • White People / genetics
  • White People / psychology


  • Serotonin Plasma Membrane Transport Proteins
  • TPH2 protein, human
  • Tryptophan Hydroxylase