Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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DOI：
10.1038/ejhg.2013.199
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发表时间：
2014-05-01
影响因子：
5.2
通讯作者：
Schumacher, Johannes
中科院分区：
文献类型：
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作者：
Becker, Jessica;Czamara, Darina;Schumacher, Johannes
阅读障碍是最常见的儿童疾病之一，学龄儿童的患病率约为 5-10%。尽管已知一个重要的遗传成分在阅读障碍的病因学中发挥作用，但我们还远未了解导致该疾病的分子机制。几个候选基因与阅读障碍有关，包括 DYX1C1、DCDC2、KIAA0319 和 MRPL19/C2ORF3 基因座，每个基因都有阳性复制和无复制的报告。我们生成了欧洲学龄儿童的跨语言样本（NeuroDys 队列），其中包括 900 多名患有阅读障碍的个体，在八个欧洲国家按照同质纳入标准进行抽样，并有相当数量的对照。在这里，我们描述了 NeuroDys 队列中阅读障碍候选基因/位点的关联分析。我们对先前报道的与阅读障碍相关的单一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关联信号，但在所有八个国家的荟萃分析中，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着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较弱的遗传效应。 2013 年 9 月 11 日在线发布
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. published online 11 September 2013