5‐HTTLPR genotype and anxiety‐related personality traits: A meta‐analysis and new data

Abstract

We investigated the strength of evidence for association of the 5-HTTLPR polymorphism and the personality trait of Harm Avoidance. We used new primary data from a large sample of adults drawn from the Finnish population. We also applied meta-analytic techniques to synthesize existing published data. The large number studies of the 5-HTTLPR polymorphism allowed us to apply a formal test of publication bias, as well as formally investigate the impact of potential moderating factors such as measurement instrument. Univariate ANOVA of primary data (n = 3,872), with 5-HTTLPR genotype as a between-groups factor, indicated no evidence of association with Harm Avoidance (p = 0.99). Meta-analysis indicated no evidence of significant association of 5-HTTLPR with Harm Avoidance (d = 0.02, p = 0.37), or EPQ Neuroticism (d = 0.01, p = 0.71), although there was evidence of association with NEO Neuroticism (d = 0.18, p < 0.001). Our analyses indicate that the 5-HTTLPR variant is not associated with Harm Avoidance. Together with our previous analyses of a large sample of participants with extreme Neuroticism scores (defined by the EPQ), we have data that excludes a meaningful genetic effect of the 5-HTTLPR on two measures of anxiety-related personality traits. There remains the possibility that the variant influences the NEO personality questionnaire measure of Neuroticism. However, a large, well-powered primary study is required to test this hypothesis directly and adequately.

Risk-Taking Behavior in a Gambling Task Associated with Variations in the Tryptophan Hydroxylase 2 Gene: Relevance to Psychiatric Disorders

“…Our findings are however consistent with the recent scientific literature, as a large meta-analysis showed that several studies have failed to show association between anxiety-related traits and 5HTTLPR, except neuroticism measured by NEO (Munafo et al, 2009): it has been argued that genetic effects on neuroticism might be complex and smaller than 1% per genetic variants (Shifman et al, 2008).…”

Evidence of association of serotonin transporter gene polymorphisms with schizophrenia in a South Indian population

“…6 These observations suggest that the short allele of 5HTTLPR has reduced promoter activity, resulting in a decreased gene expression and low serotonin uptake. 15 The short allele has been reported to have a modest role in anxiety-related personality trait 25 and suicidal behavior. 26 Within SLC6A4, STin2 has been reported to be the strongest candidate polymorphism showing susceptibility to schizophrenia.…”

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort

“…In addition to HA, ' self-directedness ' has often been correlated with serotonergic markers (Allgulander et al 1998 ;Peirson et al 1999 ;Boz et al 2007). Results from these studies should be seen as circumstantial evidence for the hypothesis and inconsistencies remain, as they do in genetic studies on HA and the serotonin system (Lesch et al 1996 ;Schinka et al 2004 ;Sen et al 2004 ;Munafò et al 2009). …”