Serotonin transporter gene promoter polymorphism (5-HTTLPR) and alcohol use in general population: interaction effect with birth cohort

Psychopharmacology (Berl). 2014 Jul;231(13):2587-94. doi: 10.1007/s00213-013-3427-8. Epub 2014 Jan 10.


Rationale and objective: Prevalence of alcohol use is markedly influenced by socioeconomic conditions and is therefore subject to cohort effects. The common genetic variation 5-HTTLPR (serotonin transporter gene-linked polymorphic region) has been related to several aspects of alcohol use and addiction but with mixed results, probably due to different environmental interaction effects. We aimed at assessing whether the association between alcohol use and 5-HTTLPR genotype is subject to cohort effects as birth cohorts may be raised in significantly different environments.

Methods: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9-year-old (recalled at ages 15 and 18) and 15-year-old (recalled at ages 18 and 25) children provided self-reports on their alcohol use in all data collection waves (complete data available n = 1,075).

Results: A significant genotype × gender × cohort interaction effect on the age of consuming the first alcoholic drink was found [F(2, 1,063) = 7.2, p < 0.001]. Females with the s/s genotype in the older cohort were the latest experimenters with alcohol, while the s/s females of younger cohort had tried alcohol earlier than any other group. In males, there was no significant cohort × genotype interaction, but the 5-HTTLPR genotype was associated with alcohol use, the s/s subjects reporting the highest consumption.

Conclusion: Expression of genetic vulnerability to alcohol use is influenced by birth cohort effects. The 5-HTTLPR genotype is associated with alcohol consumption in general population, but the effect depends on gender and birth cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Alcohol Drinking / epidemiology
  • Alcohol Drinking / genetics*
  • Child
  • Cohort Studies
  • Databases, Factual
  • Environment*
  • Estonia / epidemiology
  • Female
  • Genetic Variation
  • Genotype*
  • Humans
  • Longitudinal Studies
  • Male
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sex Factors
  • Young Adult


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins