Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits

Am J Med Genet B Neuropsychiatr Genet. 2004 May 15;127B(1):85-9. doi: 10.1002/ajmg.b.20158.


Anxiety-related personality traits, such as NEO neuroticism and TCI/TPQ harm avoidance, have been shown to have significant genetic components. To date, however, no specific genetic variants that contribute to these traits have been conclusively identified. At least 26 studies have investigated a putative association between a functional serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. The results of these studies have been inconsistent with some studies finding evidence for an association, and others not. We performed a meta-analysis of all applicable studies investigating this association. In the overall analysis (N = 5,629 subjects), we found suggestive evidence for an association between the 5-HTTLPR short allele (s) and increased anxiety-related personality trait scores (P = 0.087). However, we also found strong evidence for heterogeneity. This heterogeneity is largely explained by substantial variation between the studies in the inventory used. When the analysis was stratified by inventory type, there was a significant association between 5-HTTLPR and NEO neuroticism (P = 0.000016), a non-significant association between 5-HTTLPR and TCI/TPQ harm avoidance (P = 0.166), and no association between 5-HTTLPR and other anxiety-related personality traits (P = 0.944). There was no evidence that these results were either due to publication bias or accounted for by any one single study. We conclude that there is a strong association between the serotonin transporter promoter variant and neuroticism as measured in the NEO personality inventory and that non-replications are largely due to small sample size and the use of different inventories.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anxiety Disorders / ethnology
  • Anxiety Disorders / genetics
  • Anxiety Disorders / psychology*
  • Carrier Proteins / genetics*
  • Female
  • Genetic Heterogeneity
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Personality Inventory
  • Personality*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins