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Neural substrates of pleiotropic action of genetic variation in COMT : a meta-analysis

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2010

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Kirsch, Peter
Meyer-Lindenberg, Andreas

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https://doi.org/10.1038/mp.2009.36
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Molecular Psychiatry. 2010, 15, pp. 918-927. ISSN 1359-4184. eISSN 1476-5578. Available under: doi: 10.1038/mp.2009.36

Zusammenfassung

Genetic variation in catechol-O-methyltransferase (COMT), encoding an enzyme critical for prefrontal dopamine flux, has been studied extensively using both behavioral and neuroimaging methods. In behavior, pleiotropic action of a functional Val158Met (rs4680) polymorphism on executive cognition and emotional stability has been described and proposed to be of evolutionary significance (the 'warrior/worrier' hypothesis). We conducted a meta-analysis of all available neuroimaging studies of rs4680 to investigate the evidence for a neural substrate of this behavioral pleiotropy. We show significant association between the COMT genotype and prefrontal activation, with large (d=0.73) effect size without evidence for publication bias. Strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val), providing meta-analytical evidence for a neural substrate for the pleiotropic behavioral effects of COMT genetic variation and validating the use of intermediate phenotypes as a method to bridge between genes and behavior.

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150 Psychologie

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ISO 690MIER, Daniela, Peter KIRSCH, Andreas MEYER-LINDENBERG, 2010. Neural substrates of pleiotropic action of genetic variation in COMT : a meta-analysis. In: Molecular Psychiatry. 2010, 15, pp. 918-927. ISSN 1359-4184. eISSN 1476-5578. Available under: doi: 10.1038/mp.2009.36
BibTex
@article{Mier2010-09Neura-45669,
  year={2010},
  doi={10.1038/mp.2009.36},
  title={Neural substrates of pleiotropic action of genetic variation in COMT : a meta-analysis},
  volume={15},
  issn={1359-4184},
  journal={Molecular Psychiatry},
  pages={918--927},
  author={Mier, Daniela and Kirsch, Peter and Meyer-Lindenberg, Andreas}
}
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