Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample

Journal article


Publication Details

Author(s): Mobascher A, Diaz-Lacava A, Wagner M, Gallinat J, Wienker TF, Drichel D, Becker T, Steffens M, Dahmen N, Gruender G, Thürauf N, Kiefer F, Kornhuber J, Toliat MR, Thiele H, Nuernberg P, Steinlein O, Winterer G
Journal: PLoS ONE
Publication year: 2016
Volume: 11
Journal issue: 4
Pages range: e0152984
ISSN: 1932-6203


Abstract

Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.


FAU Authors / FAU Editors

Kornhuber, Johannes Prof. Dr. med.
Lehrstuhl für Psychiatrie und Psychotherapie
Thürauf, Norbert Prof. Dr.
Medizinische Fakultät


External institutions with authors

Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) / Federal Institute for Drugs and Medical Devices
Charité - Universitätsmedizin Berlin
Ludwig-Maximilians-Universität (LMU)
Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Universität Greifswald
Universität Köln
Universitätsklinikum Bonn
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Zentralinstitut für Seelische Gesundheit


How to cite

APA:
Mobascher, A., Diaz-Lacava, A., Wagner, M., Gallinat, J., Wienker, T.F., Drichel, D.,... Winterer, G. (2016). Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample. PLoS ONE, 11(4), e0152984. https://dx.doi.org/10.1371/journal.pone.0152984

MLA:
Mobascher, A., et al. "Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample." PLoS ONE 11.4 (2016): e0152984.

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Last updated on 2018-07-10 at 02:26