Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population

Kumakiri, Chikara; Kodama, Kazuhiro; Shimizu, Eiji; Yamanouchi, Naoto; Okada, Shinichi; Noda, S.; Okamoto, Hideki; Sato, T; Shirasawa, Hiroshi

doi:10.1016/s0304-3940(99)00098-1

Cited by 89 publications

(52 citation statements)

References 10 publications

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“…In total, 13 studies reported data on NEO neuroticism and 16 studies reported data on TCI/TPQ harm avoidance. This included three studies that reported data on both NEO neuroticism and TCI/TPQ harm avoidance 14,20,21 and two studies not reported in either the Munafò , Schinka or Sen meta-analyses. 33,35 In four studies genotype frequencies deviated significantly from HW equilibrium.…”

Section: Resultsmentioning

confidence: 99%

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

2004

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We attempted to replicate the findings of two recent meta-analyses that personality inventory moderates the association between the serotonin transporter gene and anxiety-related traits. A total of 24 studies contributed to the meta-analysis, of which three reported genotype frequencies that deviated from Hardy-Weinberg (HW) equilibrium. We found some support for the view that results depend on the type of questionnaire used, although in a direction opposite to that previously reported. Contrasts between the S/S and L/L groups were significant for TCI/TPQ harm avoidance studies (P ¼ 0.0024) but not NEO neuroticism (P ¼ 0.9757). When studies not in HW equilibrium were excluded the TCI/TPQ result for the S/S genotype still exceeded our 5% threshold, although with reduced significance (P ¼ 0.0082), and the NEO result remained nonsignificant (P ¼ 0.9109). While we cannot rule out an association between the 5HTT gene and anxiety-related traits, particularly for TCI/TPQ harm avoidance, our findings do indicate that the effect, if present, is small. Our results emphasise the importance of complete ascertainment of studies and the identification of relevant sources of heterogeneity. Molecular Psychiatry ( It is now accepted that a substantial proportion of variability in human personality is attributable to genetic variation. 1 As theories of personality propose that individual differences in specific traits are associated with individual differences in specific neurotransmitters, a number of candidate genes with known functional effects on neurotransmitter pathways have been investigated. 2 One pathway that has received considerable attention is the serotonin system, which is known to play an important role in emotional behaviour. 3 However, attempts to demonstrate an association between variation in genes involved in serotonin function and neuroticism or harm avoidance, a personality trait believed to reflect inherited differences in emotional response, have yielded inconsistent results.Even three independent meta-analyses of the large number of relevant publications do not come to a consensus: while Munafò et al 4 found little evidence for an association, both Schinka et al 5 and Sen et al 6 reported that 5HTT-LPR was significantly associated with neuroticism as measured using the class of personality questionnaires derived from Costa and McCrae's 7 five-factor model of personality (NEO-PI, NEO-PI-R, NEO-FFI), but was not associated with harm avoidance as measured using the class of questionnaires derived from Cloninger's 8 tridimensional theory of personality (TCI, TPQ).The findings of the Schinka and Sen meta-analyses are an important methodological and conceptual challenge to personality genetics. NEO neuroticism demonstrates substantial psychometric form equivalence with TCI/TPQ harm avoidance 9 and, assuming that questionnaire equivalence reflects the measurement of the same underlying biological substrate, each assessment of neuroticism should be associated with the same genetic variants. Failure to provide com...

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Section: Resultsmentioning

confidence: 99%

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

2004

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“…[7][8][9][11][12][13][14][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The characteristics of the studies are described in Table 1. Of these studies, 33 were not included in the metaanalysis.…”

Section: Description Of Studiesmentioning

confidence: 99%

“…For instance, the report by Lesch's group in 1996 5 on an association between the variation in the serotonin transporter gene and emotional stability (or neuroticism) generated much interest, [7][8][9][10] but subsequent work has delivered inconsistent conclusions. [11][12][13][14] Similar reservations surround the claims for an effect of the DRD4 gene on extraversion. 15 There are a number of possible reasons for the failure to find convincing evidence for genetic associations with personality.…”

Section: Introductionmentioning

confidence: 98%

Genetic Polymorphisms and Personality in Healthy Adults: A systematic review and meta-analysis

et al. 2003

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A meta-analysis was conducted on studies reporting data on associations between candidate genes and human personality. Studies reporting data for psychiatric populations (including organic disease and substance abuse) were excluded. A total of 46 studies contributed to the analysis. Pooled data using a fixed-effects model suggested significant associations between the 5HTT LPR, DRD4 c4t, DRD4 length, DRD2 A1/A2, DRD3 A1/A2 polymorphisms and personality traits. A multivariate analysis using a mixed-effects model and including age, sex and predominant ethnicity as covariates was applied to the analyses of 5HTT LPR and DRD4 length polymorphism data. Only the association between the 5HTT LPR polymorphism and avoidance traits remained significant (P ¼ 0.038). However, sensitivity analyses excluding data from studies reporting allele frequencies not in Hardy-Weinberg equilibrium and unpublished data resulted in this association no longer being significant. Implications for the design of future association studies of human personality are discussed, including the likely sample sizes that will be required to achieve sufficient power and the potential role of moderating variables such as sex.

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“…Thus, the original finding of higher neuroticism and harm avoidance in adult individuals with the short variant of the 5HTTLPR has been replicated and extended to younger individuals 3 and to other anxietyrelated dimensions of personality, [4][5][6] but has also failed replication. [7][8][9][10][11][12][13] Similarly, studies examining possible association between allelic variation in the promoter region of the serotonin transporter gene and risk for unipolar and bipolar depression have produced inconsistent findings (reviewed in Furlong et al 14 ). Among the potential sources for differences among these findings is the possibility that environmental variables may play an important role in the functional expression of the genotype.…”

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confidence: 99%

Early experience and serotonin transporter gene variation interact to influence primate CNS function

et al. 2002

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Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

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Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population

Cited by 89 publications

References 10 publications

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Genetic Polymorphisms and Personality in Healthy Adults: A systematic review and meta-analysis

Early experience and serotonin transporter gene variation interact to influence primate CNS function

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