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  Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating

Quednow, B. B., Brinkmeyer, J., Mobascher, A., Nothnagel, M., Musso, F., Grunder, G., et al. (2012). Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating. Proceedings of the National Academy of Sciences of the United States of America, 109(16), 6271-6276. doi:10.1073/pnas.1118051109.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC7E-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EC7F-3
Genre: Journal Article

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© 2012 National Academy of Sciences
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 Creators:
Quednow, B. B., Author
Brinkmeyer, J., Author
Mobascher, A., Author
Nothnagel, M., Author
Musso, F., Author
Grunder, G., Author
Savary, N., Author
Petrovsky, N., Author
Frommann, I., Author
Lennertz, L., Author
Spreckelmeyer, K. N., Author
Wienker, T. F.1, 2, Author              
Dahmen, N., Author
Thuerauf, N., Author
Clepce, M., Author
Kiefer, F., Author
Majic, T., Author
Mossner, R., Author
Maier, W., Author
Gallinat, J., Author
Diaz-Lacava, A., AuthorToliat, M. R., AuthorThiele, H., AuthorNürnberg, P., AuthorWagner, M., AuthorWinterer, G., Author more..
Affiliations:
1Clinical Genetics (Thomas F. Wienker), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479643              
2Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany, ou_persistent22              

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Free keywords: single nucleotide polymorphism intermediate phenotype nicotine gene–environment interaction
 Abstract: Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential. Although sensorimotor gating and sensory gating are not identical, recent data suggest that they share genetic fundamentals. In a multicenter study at six academic institutions throughout Germany, we applied an auditory P50 suppression paradigm to 1,821 subjects (1,023 never-smokers, 798 smokers) randomly selected from the general population. Samples were genotyped for 21 TCF4 polymorphisms. Given that smoking is highly prevalent in schizophrenia and affects sensory gating, we also assessed smoking behavior, cotinine plasma concentrations, exhaled carbon monoxide, and the Fagerstrom Test (FTND). P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002-0.00005). These gene effects were modulated by smoking behavior as indicated by significant interactions of TCF4 genotype and smoking status; heavy smokers (FTND score >/= 4) showed stronger gene effects on P50 suppression than light smokers and never-smokers. Our finding suggests that sensory gating is modulated by an interaction of TCF4 genotype with smoking, and both factors may play a role in early information processing deficits also in schizophrenia. Consequently, considering smoking behavior may facilitate the search for genetic risk factors for schizophrenia.

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Language(s): eng - English
 Dates: 2012-03-262012-04-17
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1118051109
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: National Academy of Sciences
Pages: - Volume / Issue: 109 (16) Sequence Number: - Start / End Page: 6271 - 6276 Identifier: ISSN: 0027-8424
CoNE: /journals/resource/954925427230