Association of the 5- HTTLPR genotype and unipolar depression: a meta-analysis

Psychol Med. 2010 Nov;40(11):1767-78. doi: 10.1017/S0033291710000516. Epub 2010 Apr 12.


Background: We sought to ascertain the strength of evidence for association between the 5-HTTLPR polymorphism and unipolar depression.

Method: We applied meta-analytic techniques to data from relevant published studies, and obtained an estimate of the likely magnitude of effect of any association. We also tested for possible publication bias, and explored the impact of various study design characteristics on the magnitude of the observed effect size.

Results: Meta-analysis indicated evidence of a small but statistically significant association between the 5-HTTLPR polymorphism and unipolar depression [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.03-1.12]. This remained significant when data from samples of European and East Asian ancestry were analyzed separately. In all cases there was evidence of significant between-study heterogeneity, although the observed associations were robust to the application of a random-effects framework.

Conclusions: Our results support the presence of a small effect of a polymorphism in the serotonin transporter promoter on susceptibility to depression. However, we caution that it is possible that the effect has an artifactual basis, rather than a biological origin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chi-Square Distribution
  • Confidence Intervals
  • Depressive Disorder / etiology
  • Depressive Disorder / genetics*
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Odds Ratio
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins