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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort

机译:欧洲跨语言NeuroDys队列中阅读障碍候选基因的遗传分析

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摘要

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.
机译:阅读障碍是最常见的儿童疾病之一,在学龄儿童中患病率约为5-10%。尽管已知一种重要的遗传成分在阅读障碍的病因中起着作用,但我们距离导致这种疾病的分子机制还很远。已经有几种候选基因与阅读障碍有关,包括DYX1C1,DCDC2,KIAA0319和MRPL19 / C2ORF3基因座,每一个都有阳性和无复制的报道。我们生成了一个欧洲跨语言样本的学龄儿童-NeuroDys队列-包括900多名患有阅读障碍的个体,并在8个欧洲国家/地区采用了均一的纳入标准,并进行了相当数量的对照。在这里,我们描述了NeuroDys队列中阅读障碍候选基因/基因座的关联分析。我们对以前据报道与阅读障碍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关联信号,但在所有八个国家的荟萃分析中,没有发现与病例对照状态或单词阅读或拼写的定量测量有显着关联的任何标记或单倍型。像其他神经认知障碍一样,我们的发现强调需要更大的样本量来验证可能的弱遗传效应。

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