A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety.
Abstract
Studies of the association between polymorphisms of the serotonin transporter gene (5-HTT) and trait anxiety have produced inconsistent results, raising questions about the strength of the relationship and the methodological conditions under which the relationship holds. We conducted a meta-analysis of existing studies to provide formal statistical measures of the strength of the linked polymorphic region of the serotonin transporter gene (5-HTTLPR)-anxiety relationship. For the entire collection of 26 studies, results provided no support for a relationship between anxiety and the presence of the short form of the 5-HTTLPR polymorphism. There was strong evidence of the presence of moderating variables, however, and subsequent analysis revealed that choice of the measure of trait anxiety was significant. Studies using the Neuroticism scale of Costa and McCrae were found to produce a small positive effect (d=0.23). Other potential moderators (country of study origin, type of subject) did not have a meaningful impact on d statistics. These findings indicate that 5-HTTLPR may in fact have a small but reliable influence on personality, particularly in the manifestation of trait anxiety when measured with a neuroticism scale based on the five-factor model of personality. Our results suggest that the success of future personality genetics research will be maximized by the use of personality measures from both the psychobiological and five-factor models.
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Genetic association studies for complex phenotypes such as social behavior can be highly sensitive to measurement construct.
“Genetic association studies for complex phenotypes such as social behavior can be highly sensitive to measurement construct. For example, a meta-analysis reviewing association for a serotonin transporter gene polymorphism (5-HTTLPR) and anxiety related traits demonstrated how choice of measurement scale may be a critical factor in moderating phenotypic contours[32].”
From The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task (2009) · cites this paper as [32]
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- Authors
- Schinka, J. A., Busch, R. M., & Robichaux-Keene, N.
- Affiliations
- United States Department of Veterans Affairs (US)
- Corresponding author
- Schinka, J A
- ORCID
- Busch, R M
- Venue
- Molecular Psychiatry
- Published
- 2004-01-27
- Volume
- 9
- Issue
- 2
- Pages
- 197-202
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1997746844
- Cited by
- 521
- References
- 54
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 10 · 2020: 55 · 2019: 10 · 2018: 12 · 2017: 15 · 2016: 19 · 2015: 19 · 2014: 23 · 2013: 33 · 2012: 33
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- serotonin transporter gene, 5-HTTLPR polymorphism, trait anxiety, neuroticism, five-factor model of personality, personality genetics, gene-environment association, moderators, personality measures
- MeSH terms
- Anxiety, Carrier Proteins, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Personality, Polymorphism, Genetic, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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