Open AccessATP 2C2 and DYX 1C1 are putative modulators of dyslexia‐related MMR
Author(s) -
Müller Bent,
Schaadt Gesa,
Boltze Johannes,
Emmrich Frank,
Skeide Michael A.,
Neef Nicole E.,
Kraft Indra,
Brauer Jens,
Friederici Angela D.,
Kirsten Holger,
Wilcke Arndt
Publication year - 2017
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.851
Subject(s) - dyslexia , psychology , endophenotype , spelling , single nucleotide polymorphism , biological theories of dyslexia , snp , genetics , developmental psychology , audiology , cognitive psychology , reading (process) , biology , cognition , neuroscience , medicine , gene , developmental dyslexia , genotype , linguistics , philosophy , political science , law
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 MMR s with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms ( SNP s) within 10 genes. Results First, we demonstrated validity of these SNP s 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 SNP s that is associated with the dyslexia‐specific late component of MMR . In total, four independent SNP s within DYX 1C1 and ATP 2C 2 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 eQTL s. Conclusion Our findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNP s, the late component of MMR and dyslexia.