Müller, Bent, Schaadt, Gesa, Boltze, Johannes, Emmrich, Frank, Skeide, Michael A., Neef, Nicole E., Kraft, Indra, Brauer, Jens, Friederici, Angela D., Kirsten, Holger and Wilcke, Arndt (2017) ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR. Brain and Behavior, 7 (11). e00851. doi:10.1002/brb3.851 ISSN 2162-3279.

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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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Dyslexia, Auditory perception, Reading, Electroencephalography
Journal or Publication Title:	Brain and Behavior
Publisher:	John Wiley & Sons Ltd.
ISSN:	2162-3279
Official Date:	18 October 2017
Dates:	Date Event 18 October 2017 Published 1 September 2017 Accepted
Volume:	7
Number:	11
Page Range:	e00851
DOI:	10.1002/brb3.851
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	14 June 2019
Date of first compliant Open Access:	14 June 2019
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED Fraunhofer-Gesellschaft http://dx.doi.org/10.13039/501100003185 UNSPECIFIED Max-Planck-Gesellschaft http://dx.doi.org/10.13039/501100004189 UNSPECIFIED Leipzig Interdisciplinary Research Cluster of Genetic Factors, Clinical Phenotypes and Environment UNSPECIFIED

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