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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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Müller_Schaadt_2017.pdf (Verlagsversion), 631KB
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 Urheber:
Müller, Bent1, Autor
Schaadt, Gesa2, 3, Autor           
Boltze, Johannes1, 4, 5, Autor
Emmrich, Frank1, Autor
LEGASCREEN Consortium, Autor              
Skeide, Michael A.2, Autor           
Neef, Nicole2, Autor           
Kraft, Indra2, Autor           
Brauer, Jens2, Autor           
Friederici, Angela D.2, Autor           
Kirsten, Holger1, 6, 7, Autor
Wilcke, Arndt1, Autor
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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Schlagwörter: Auditory discrimination; Child; Dyslexia; Electroencephalography; eQTL ; Genetic predisposition to disease; German language; Intermediate phenotype; Mismatch negativity; Single-nucleotide polymorphism
 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2017-08-232016-05-302017-09-012017-10-18
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1002/brb3.851
PMID: 29201552
PMC: PMC5698869
Anderer: eCollection 2017
 Art des Abschluß: -

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

Quelle 1

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Titel: Brain and Behavior
  Kurztitel : Brain Behav
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Hoboken, NJ : John Wiley & Sons
Seiten: - Band / Heft: 7 (11) Artikelnummer: e00851 Start- / Endseite: - Identifikator: ISSN: 2162-3279 (e-only)
CoNE: https://pure.mpg.de/cone/journals/resource/2162-3279