Twin Research and Human Genetics

Articles

The Serotonin Transporter Gene Length Polymorphism (5-HTTLPR) and Life Events: No Evidence for an Interaction Effect on Neuroticism and Anxious Depressive Symptoms

Christel M. Middeldorpa1 c1, Eco J. C. de Geusa2, Gonneke Willemsena3, Jouke-Jan Hottengaa4, P. Eline Slagbooma5 and Dorret I. Boomsmaa6

a1 Department of Biological Psychology, VU University Amsterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Academic Medical Center, Amsterdam, The Netherlands; Department of Child and Adolescent Psychiatry, GGZ inGeest/VU Medical Center, Amsterdam, The Netherlands. cm.middeldorp@psy.vu.nl

a2 Department of Biological Psychology, VU University Amsterdam, The Netherlands.

a3 Department of Biological Psychology, VU University Amsterdam, The Netherlands.

a4 Department of Biological Psychology, VU University Amsterdam, The Netherlands.

a5 Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

a6 Department of Biological Psychology, VU University Amsterdam, The Netherlands.

Abstract

The finding of a significant gene by environment interaction effect on depression of the serotonin transporter length polymorphism (5-HTTLPR) and the Number of experienced Life Events (NLE) was not replicated in two large meta-analyses (Munafo et al., 2009; Risch et al., 2009). These meta-analyses have been criticized on the grounds that large studies that get most weight in meta-analyses have the poorest measurement quality of life events and, as a consequence, do not find an effect. Another issue is the time frame across which the NLE are measured. Proximal life events appear to be better predictors of depression than more distal events. We present the results of analyses of the 5-HTTLPR × NLE effect on anxious depression and neuroticism scores in a sample of 1,155 twins and their parents and siblings from 438 families. The interaction effect was tested separately for NLE experienced across the life span and NLE experienced in the past year. There was a significant main effect of NLE on anxious depression and neuroticism, especially when these were experienced in the past year. No interaction with 5-HTTLPR was found for NLE either experienced across the life span or across the past year. Our results support the two recent meta-analyses. Given recent insights from genome wide association studies, it seems more useful to focus on the joint effect of several genes, that are, for example, part of the same biological pathway, in interaction with the environment, than on one candidate gene.

(Received August 04 2010)

(Accepted September 27 2010)

Keywords

  • anxiety;
  • depression;
  • serotonin transporter gene;
  • life events;
  • gene environment interaction

Correspondence:

c1 Address for correspondence: Christel Middeldorp, Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, the Netherlands.

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