Universität zu Köln

Mobascher, A., Diaz-Lacava, A., Wagner, M., Gallinat, J., Wienker, T. F., Drichel, D., Becker, T., Steffens, M., Dahmen, N., Gruender, G., Thuerauf, N., Kiefer, F., Kornhuber, J., Toliat, M. R., Thiele, H., Nuernberg, P., Steinlein, O. and 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). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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 odd-ball. 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 thatmay be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activitymeasures 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mobascher, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diaz-Lacava, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gallinat, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wienker, T. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Drichel, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steffens, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahmen, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruender, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thuerauf, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiefer, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornhuber, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinlein, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Winterer, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278828
DOI:	10.1371/journal.pone.0152984
Journal or Publication Title:	PLoS One
Volume:	11
Number:	4
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTERIOR CINGULATE CORTEX; INTRACEREBRAL POTENTIALS; WORKING-MEMORY; VISUAL-STIMULI; RARE TARGET; ELECTROMAGNETIC TOMOGRAPHY; VISUOSPATIAL ATTENTION; RESPONSE SPEED; CHRNA4 GENE; SCHIZOPHRENIA Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27882