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Eur Neuropsychopharmacol. 2016 Jan;26(1):150-5. doi: 10.1016/j.euroneuro.2015.11.007. Epub 2015 Nov 14.

Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample.

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  • 1Department of Psychiatry and Psychotherapy, University of Bonn, Germany. Electronic address:
  • 2Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
  • 3Department of Psychology, University of Bonn, Germany.
  • 4Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Germany.
  • 5Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany.
  • 6Department of Psychiatry and Psychotherapy, RWTH Aachen University, and JARA -Translational Brain Medicine, Germany.
  • 7Max-Planck Institute for Molecular Genetics, Berlin, Germany.
  • 8Department of Psychiatry, Johannes Gutenberg University Mainz, Germany.
  • 9Department of Psychiatry, Friedrich-Alexander University Erlangen-Nuernberg, Germany.
  • 10Department of Addictive Behavior and Addictive Medicine, Central Institute of Mental Health, Germany.
  • 11Cologne Center of Genomics, University of Cologne, Germany.
  • 12Experimental and Clinical Research Center (ECRC), Charité - University Medicine Berlin, Germany.
  • 13Department of Psychiatry and Psychotherapy, University of Bonn, Germany; DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany.


Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected in the context of the German multi-centre study ׳Genetics of Nicotine Dependence and Neurobiological Phenotypes׳. Homozygous carriers of the C-allele showed significantly higher levels of harm avoidance than homozygous T-allele carriers, with heterozygous subjects exhibiting intermediate scores. The effect was neither modulated by age or gender nor by smoking status. By replicating previous findings in a large population-based sample for the first time, the present study adds to the growing evidence suggesting an involvement of nicotinic cholinergic mechanism in anxiety and negative emotionality, which may pose an effective target for medical treatment.


CHRNA4; Harm avoidance; Nicotine; Rs1044396; TCI

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