Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.
Becker , J , Czamara , D , Scerri , T S , Ramus , F , Csépe , V , Talcott , J B , Stein , J , Morris , A , Ludwig , K U , Hoffmann , P , Honbolygó , F , Tóth , D , Fauchereau , F , Bogliotti , C , Iannuzzi , S , Chaix , Y , Valdois , S , Billard , C , George , F , Soares-Boucaud , I , Gérard , C-L , van der Mark , S , Schulz , E , Vaessen , A , Maurer , U , Lohvansuu , K , Lyytinen , H , Zucchelli , M , Brandeis , D , Blomert , L , Leppänen , P H , Bruder , J , Monaco , A P , Müller-Myhsok , B , Kere , J , Landerl , K , Nöthen , M M , Schulte-Körne , G , Paracchini , S , Peyrard-Janvid , M & Schumacher , J 2014 , ' Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort ' , European Journal of Human Genetics , vol. 22 , no. 5 , pp. 675-680 . https://doi.org/10.1038/ejhg.2013.199
European Journal of Human Genetics
© 2014, Macmillan Publishers Ltd. All rights reserved. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at www.nature.com / https://dx.doi.org/10.1038/ejhg.2013.199
DescriptionThe work conducted at the WTCHG was supported by Wellcome Trust grants [076566/Z/05/Z] and [075491/Z/04]; the work in Zurich partly by an SNSF grant [32-108130]. We also thank MAF (Mutation Analysis core Facility) at the Karolinska Institute, Novum, Huddinge. The French part of the project was funded by Agence Nationale de la Recherche (ANR-06-NEURO-019-01 GENEDYS) and Ville de Paris. S Paracchini is a Royal Society University Research Fellow. D Czamara was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy).
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