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

TY - JOUR

T1 - Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample

AU - Bey, Katharina

AU - Lennertz, Leonhard

AU - Markett, Sebastian

AU - Petrovsky, Nadine

AU - Gallinat, Jürgen

AU - Gründer, Gerhard

AU - Spreckelmeyer, Katja N

AU - Wienker, Thomas F

AU - Mobascher, Arian

AU - Dahmen, Norbert

AU - Thuerauf, Norbert

AU - Kornhuber, Johannes

AU - Kiefer, Falk

AU - Toliat, Mohammad R

AU - Nürnberg, Peter

AU - Winterer, Georg

AU - Wagner, Michael

N1 - Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.euroneuro.2015.11.007

DO - 10.1016/j.euroneuro.2015.11.007

M3 - SCORING: Journal article

C2 - 26612384

VL - 26

SP - 150

EP - 155

JO - EUR NEUROPSYCHOPHARM

JF - EUR NEUROPSYCHOPHARM

SN - 0924-977X

IS - 1

ER -