Elsevier

Biological Psychiatry

Volume 58, Issue 6, 15 September 2005, Pages 451-456
Biological Psychiatry

Original article
The Serotonin Transporter Length Polymorphism, Neuroticism, and Depression: A Comprehensive Assessment of Association

https://doi.org/10.1016/j.biopsych.2005.04.050Get rights and content

Background

A promoter-based length polymorphism (5-HTTLPR) of the human serotonin gene (SLC6A4) has exhibited inconsistent association with emotionality phenotypes, such as major depression (MD) and the personality trait neuroticism (N). Several explanations have been posited to account for this discrepancy, including underpowered experimental design and variation in gender ratio, age, and ethnicity.

Methods

Here, we describe three independent tests of association between the 5-HTTLPR locus and both N and MD in samples selected for extremeness of N-score from two homogenous populations (n = 88,142, and 20,921). Calculations of statistical power indicated that at a 5% α level, these samples retain 100% power to detect a genetic effect accounting for just .5% of phenotypic variance. Effects of age were regressed out of the phenotypic measure, and gender was included as a covariate.

Results

No statistically significant effects of genotype could be identified on either N or MD phenotypes (in all cases, p ≥ .26), independently of the genetic mode of action applied.

Conclusions

Our data do not support the hypothesis that the 5-HTTLPR variant contributes significantly toward human emotionality as indexed by either the Eysenck Personality Questionnaire N scale or the DSM-IV for MD.

Section snippets

Subjects

The Eysenck Personality Questionnaire (EPQ; Eysenck and Eysenck 1975), a 90-item self-report binary response format questionnaire, was used to evaluate the personality trait neuroticism (N) in a large nonclinical population from southwestern England (n = 88,142). Within this sample, N was distributed normally (skewness = −.02, SE = .01; kurtosis = −.95, SE = .02), and consistent with previous reports (Lynn and Martin 1997), mean N score was elevated in female (μ = 12.66, SD = 5.66) relative to

Power Calculations

Power analyses, conducted by simulation on both the singleton and EPIC-Norfolk samples, indicate that these investigations have sufficient power to detect extremely small effects on the N phenotype. At a significance threshold of .05, the singleton sample held 100% power to detect a genetic effect accounting for .5% of phenotypic variation and 95.3% power to detect an effect size of just .25%. At an equivalent threshold, the EPIC-Norfolk sample retained 100% power to detect an effect size of

Discussion

In this report, we have described a large-scale analysis of genetic association between the SLC6A4 promoter polymorphism (5-HTTLPR) and the personality trait N (quantified with the EPQ), in addition to both MD and RMD phenotypes (defined according to DSM-IV [American Psychiatric Association 1994]). While controlling for both age and gender and using only populations predominantly homogeneous in ethnicity, we found no evidence to indicate the involvement of this variant in the genetic

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