Becker Jessica, Czamara Darina, Scerri Tom S, Ramus Franck, Csépe Valéria, Talcott Joel B, Stein John, Morris Andrew, Ludwig Kerstin U, Hoffmann Per, Honbolygó Ferenc, Tóth Dénes, Fauchereau Fabien, Bogliotti Caroline, Iannuzzi Stéphanie, Chaix Yves, Valdois Sylviane, Billard Catherine, George Florence, Soares-Boucaud Isabelle, Gérard Christophe-Loïc, van der Mark Sanne, Schulz Enrico, Vaessen Anniek, Maurer Urs, Lohvansuu Kaisa, Lyytinen Heikki, Zucchelli Marco, Brandeis Daniel, Blomert Leo, Leppänen Paavo H T, Bruder Jennifer, Monaco Anthony P, Müller-Myhsok Bertram, Kere Juha, Landerl Karin, Nöthen Markus M, Schulte-Körne Gerd, Paracchini Silvia, Peyrard-Janvid Myriam, Schumacher Johannes
1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
1] Max Planck Institute of Psychiatry, Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Eur J Hum Genet. 2014 May;22(5):675-80. doi: 10.1038/ejhg.2013.199. Epub 2013 Sep 11.
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.
诵读困难是最常见的儿童疾病之一，在学龄儿童中的患病率约为5%-10%。虽然已知重要的遗传因素在诵读困难的病因中起作用，但我们远未了解导致该疾病的分子机制。几个候选基因与诵读困难有关，包括DYX1C1、DCDC2、KIAA0319和MRPL19/C2ORF3基因座，每个基因座都有阳性和未重复的报道。我们建立了一个欧洲学龄儿童跨语言样本——NeuroDys队列，其中包括900多名诵读困难个体，按照统一的纳入标准从八个欧洲国家进行抽样，并抽取了数量相当的对照组。在此，我们描述了NeuroDys队列中诵读困难候选基因/基因座的关联分析。我们对先前报道与诵读困难相关的单个标记和单倍型进行了病例对照和定量关联分析。尽管我们在单个国家的样本中观察到了关联信号，但在对所有八个国家进行的荟萃分析中，我们没有发现任何与病例对照状态或单词阅读或拼写的定量测量显著相关的标记或单倍型。与其他神经认知障碍一样，我们的研究结果强调需要更大的样本量来验证可能微弱的遗传效应。
