Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT)

Abstract

Keywords: personality; polymorphism; tridimensional personality questionnaire; catechol O-methyltransferase; dopamine D4 receptor; serotonin transporter promoter Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol Omethyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT × 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR × D4DR (F = 6.18, P = 0.03) and COMT × 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry Twin studies demonstrate that personality traits measured by several self-report questionnaires including the TPQ 1 and NEO-PI-R 2 are partially inherited and between 30-60% of the observed variance can be accounted for by genes. Only recently, however, have common genetic polymorphisms especially DRD4 and 5-HTTLPR, been provisionally assigned to particular temperament factors. [3][4][5] It seems reasonable that as additional genetic information is inventoried for various cohorts, associations between DRD4, 5-HTTLPR and other candidate genes and complex phenotypes will be further clarified. We, 6-8 and others, 9-11 have begun to examine multiple interactions between common genetic polymorphisms and complex behavioral traits. The catechol O-methyltransferase (COMT) gene contains a common, functional polymorphism in which a val-to-met amino acid substitution markedly reduces enzyme activity to about 20% of wild-type (val) levels. 12 Recent studies have suggested a role for COMT in behaviors often associated with impulsivity and disinhibition, 13-15 although to our knowledge, this gene has yet to be examined for a role in normal human personality.In the current study we initially examined using multivariate ANOVA four TPQ personality factor scores for 455 subjects grouped by three polymo...

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

“…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.…”

“…33,35 In four studies genotype frequencies deviated significantly from HW equilibrium. 11,18,24,31 In one study 21 there was insufficient data to test for departure from HW equilibrium. In two studies data were not reported in a format that enabled their inclusion in the subsequent meta-analysis 28,31 and attempts to contact the authors of these studies to request data in an appropriate format were unsuccessful.…”

Gene–gene effects on central processing of aversive stimuli

“…increment in trait anxiety. Such weak associations may easily escape replication 32 and elude attempts to quantify combined gene effects or the impact of gene  gene interactions [33][34][35] on personality.…”

Further evidence for a modulation of Novelty Seeking by DRD4 exon III, 5-HTTLPR, and COMT val/met variants

“…Since the expression of a behavioral phenotype is influenced by the developmental and physiologic effect of multiple gene variants, Benjamin et al 6 suggested 'that failure to replicate associations between personality factors and some genes may be partially due to the presence of additional modifying common polymorphisms' (Benjamin et al, 6 p 98). This view is based on their finding that in the absence of the short (s) allele of the serotonin transporter gene promoter-linked polymorphic region (5-HTTLPR) 7 and in the presence of the val/val genotype of the catechol O-methyltransferase gene (COMT) val/met polymorphism, 8 Novelty Seeking scores are higher in the presence of the DRD4 exon III 7-repeat allele.…”

“…This view is based on their finding that in the absence of the short (s) allele of the serotonin transporter gene promoter-linked polymorphic region (5-HTTLPR) 7 and in the presence of the val/val genotype of the catechol O-methyltransferase gene (COMT) val/met polymorphism, 8 Novelty Seeking scores are higher in the presence of the DRD4 exon III 7-repeat allele. 6 In order to examine, whether our failure to replicate the proposed association in our recent study 5 may, in part, be accounted for by the action of other genetic variants not included in the initial analyses, we followed the methodology of Benjamin et al 6 and also genotyped our sample for 5-HTTLPR and the COMT val/met polymorphism. For analysis of gene-gene interaction, all three genotypes were available from 280 unrelated healthy volunteers of German ethnicity (212 women and 68 men; mean age: 21.973.9 years, age range: 18-41 years).…”