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  ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR

Müller, B., Schaadt, G., Boltze, J., Emmrich, F., LEGASCREEN Consortium, Skeide, M. A., et al. (2017). ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR. Brain and Behavior, 7(11): e00851. doi:10.1002/brb3.851.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-FC78-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-5313-8
Genre: Journal Article

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 Creators:
Müller, Bent1, Author
Schaadt, Gesa2, 3, Author              
Boltze, Johannes1, 4, 5, Author
Emmrich, Frank1, Author
LEGASCREEN Consortium, Author              
Skeide, Michael A.2, Author              
Neef, Nicole2, Author              
Kraft, Indra2, Author              
Brauer, Jens2, Author              
Friederici, Angela D.2, Author              
Kirsten, Holger1, 6, 7, Author
Wilcke, Arndt1, Author
Affiliations:
1Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany, ou_persistent22              
2Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634551              
3Department of Psychology, Humboldt University Berlin, Germany, ou_persistent22              
4Department of Medical Cell Technology, Fraunhofer Institute for Marine Biotechnology, Lübeck, Germany, ou_persistent22              
5University of Lübeck, Germany, ou_persistent22              
6Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany, ou_persistent22              
7Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Germany, ou_persistent22              

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Free keywords: Auditory discrimination; Child; Dyslexia; Electroencephalography; eQTL ; Genetic predisposition to disease; German language; Intermediate phenotype; Mismatch negativity; Single-nucleotide polymorphism
 Abstract: Background Dyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German-speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event-related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input. Methods In this study, we comprehensively analyzed associations of dyslexia-specific late MMRs with genetic variants previously reported to be associated with dyslexia-related phenotypes in multiple studies comprising 25 independent single-nucleotide polymorphisms (SNPs) within 10 genes. Results First, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia-specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue-specific expression analysis and eQTLs. Conclusion Our findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia-related SNPs, the late component of MMR and dyslexia.

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Language(s): eng - English
 Dates: 2017-08-232016-05-302017-09-012017-10-18
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/brb3.851
PMID: 29201552
PMC: PMC5698869
Other: eCollection 2017
 Degree: -

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Funding program : Leipzig Interdisciplinary Research Cluster of Genetic Factors, Clinical Phenotypes and Environment
Funding organization : LIFE – Leipzig Research Center for Civilization Diseases at the University of Leipzig
Project name : Legascreen
Grant ID : M.FE.A.NEPF0001
Funding program : -
Funding organization : Fraunhofer Society and the Max Planck Society

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Title: Brain and Behavior
  Abbreviation : Brain Behav
Source Genre: Journal
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Publ. Info: Hoboken, NJ : John Wiley & Sons
Pages: - Volume / Issue: 7 (11) Sequence Number: e00851 Start / End Page: - Identifier: ISSN: 2162-3279 (e-only)
CoNE: https://pure.mpg.de/cone/journals/resource/2162-3279