title: Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany. Electronic address: katharina.bey@ukb.uni-bonn.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bey
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Lennertz
authors.affiliation: Department of Psychology, University of Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Markett
authors.affiliation: Department of Psychology, University of Bonn, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry and Psychotherapy, RWTH Aachen University, and JARA -Translational Brain Medicine, Germany.
authors.forename: Katja N
authors.initials: KN
authors.lastname: Spreckelmeyer
authors.affiliation: Max-Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.affiliation: Department of Psychiatry, Johannes Gutenberg University Mainz, Germany.
authors.forename: Arian
authors.initials: A
authors.lastname: Mobascher
authors.affiliation: Department of Psychiatry, Johannes Gutenberg University Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.affiliation: Department of Psychiatry, Friedrich-Alexander University Erlangen-Nuernberg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Thuerauf
authors.affiliation: Department of Psychiatry, Friedrich-Alexander University Erlangen-Nuernberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Addictive Behavior and Addictive Medicine, Central Institute of Mental Health, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.affiliation: Cologne Center of Genomics, University of Cologne, Germany.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Toliat
authors.affiliation: Cologne Center of Genomics, University of Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Experimental and Clinical Research Center (ECRC), Charité - University Medicine Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany; DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D005858:Germany; D040261:Harm Reduction; D006801:Humans; D008297:Male; D010551:Personality / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics
chemical_list: D011978:Receptors, Nicotinic
keywords: CHRNA4; Harm avoidance; Nicotine; Rs1044396; TCI