Variants of the serotonin transporter gene and NEO-PI-R neuroticism: No association in the BLSA and SardiNIA samples

Antonio Terracciano, Lenuta Balaci, Jason Thayer, Matthew Scally, Sarah Kokinos, Luigi Ferrucci, Toshiko Tanaka, Alan B. Zonderman, Serena Sanna, Nazario Olla, Maria Antonietta Zuncheddu, Silvia Naitza, Fabio Busonero, Manuela Uda, David Schlessinger, Gonçalo R. Abecasis, Paul T. Costa

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The polymorphism in the serotonin transporter gene promoter region (5-HTTLPR) is by far the most studied variant hypothesized to influence Neuroticism-related personality traits. The results of previous studies have been mixed and appear moderated by the personality questionnaire used. Studies that used the TCI to assess Harm Avoidance or the EPQ to assess Neuroticism have found no association with the 5-HTTLPR. However, studies that used the NEO-PI-R or related instruments (NEO-PI, NEOFFI) to measure Neuroticism have found some evidence of association. This study examines the association of variants in the serotonin transporter gene in a sample from a genetically isolated population within Sardinia (Italy) that is several times larger than previous samples that used the NEO-PI-R (N = 3,913). The association was also tested in a sample (N = 548) from the Baltimore Longitudinal Study of Aging (BLSA), in which repeatedNEO-PI-R assessments were obtained. In the SardiNIA sample, we found no significant association of the5-HTTLPRgenotypes with Neuroticism or its facets (Anxiety, Angry-Hostility, Depression, Self-Consciousness, Impulsiveness, and Vulnerability). In the BLSA sample, we found lower scores on Neuroticism traits for the heterozygous group, which is inconsistent with previous studies. We also examined eight SNPs in the SardiNIA (N=3,972) and nine SNPs in the BLSA (N=1,182) that map within or near the serotonin transporter gene (SLC6A4), and found no association. Along with other large studies that used different phenotypic measures and found no association, this study substantially increases the evidence against a link between 5-HTT variants and Neuroticism-related traits.

Original languageEnglish (US)
Pages (from-to)1070-1077
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number8
StatePublished - Dec 5 2009
Externally publishedYes


  • 5-HTT
  • Anxiety
  • Depression
  • GWA
  • Personality

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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