Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample
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Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample. / Mobascher, A; Diaz-Lacava, A; Wagner, M; Gallinat, J; Wienker, T F; Drichel, D; Becker, T; Steffens, M; Dahmen, N; Gründer, G; Thürauf, N; Kiefer, F; Kornhuber, J; Toliat, M R; Thiele, H; Nürnberg, P; Steinlein, O; Winterer, G.
in: PLOS ONE, Jahrgang 11, Nr. 4, 2016, S. e0152984.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample
AU - Mobascher, A
AU - Diaz-Lacava, A
AU - Wagner, M
AU - Gallinat, J
AU - Wienker, T F
AU - Drichel, D
AU - Becker, T
AU - Steffens, M
AU - Dahmen, N
AU - Gründer, G
AU - Thürauf, N
AU - Kiefer, F
AU - Kornhuber, J
AU - Toliat, M R
AU - Thiele, H
AU - Nürnberg, P
AU - Steinlein, O
AU - Winterer, G
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Adult
KW - Electrophysiological Phenomena
KW - Endophenotypes
KW - Female
KW - Germany
KW - Humans
KW - Male
KW - Neuroimaging
KW - Polymorphism, Single Nucleotide
KW - Receptors, Nicotinic
KW - Smoking
KW - Tobacco Use Disorder
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0152984
DO - 10.1371/journal.pone.0152984
M3 - SCORING: Journal article
C2 - 27054571
VL - 11
SP - e0152984
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 4
ER -
