Carrion-Castillo Amaia, Maassen Ben, Franke Barbara, Heister Angelien, Naber Marlies, van der Leij Aryan, Francks Clyde, Fisher Simon E
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Centre for Language and Cognition Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Hum Genet. 2017 Apr;25(4):452-460. doi: 10.1038/ejhg.2016.194. Epub 2017 Jan 11.
Dyslexia is a common specific learning disability with a substantive genetic component. Several candidate genes have been proposed to be implicated in dyslexia susceptibility, such as DYX1C1, ROBO1, KIAA0319, and DCDC2. Associations with variants in these genes have also been reported with a variety of psychometric measures tapping into the underlying processes that might be impaired in dyslexic people. In this study, we first conducted a literature review to select single nucleotide polymorphisms (SNPs) in dyslexia candidate genes that had been repeatedly implicated across studies. We then assessed the SNPs for association in the richly phenotyped longitudinal data set from the Dutch Dyslexia Program. We tested for association with several quantitative traits, including word and nonword reading fluency, rapid naming, phoneme deletion, and nonword repetition. In this, we took advantage of the longitudinal nature of the sample to examine if associations were stable across four educational time-points (from 7 to 12 years). Two SNPs in the KIAA0319 gene were nominally associated with rapid naming, and these associations were stable across different ages. Genetic association analysis with complex cognitive traits can be enriched through the use of longitudinal information on trait development.
阅读障碍是一种常见的特定学习障碍，具有重要的遗传成分。已经提出了几个候选基因与阅读障碍易感性有关，如DYX1C1、ROBO1、KIAA0319和DCDC2。这些基因的变异与各种心理测量指标之间的关联也有报道，这些指标涉及阅读障碍患者可能受损的潜在过程。在本研究中，我们首先进行了文献综述，以选择在多项研究中反复涉及的阅读障碍候选基因中的单核苷酸多态性（SNP）。然后，我们在来自荷兰阅读障碍项目的丰富表型纵向数据集中评估这些SNP的关联性。我们测试了与几个定量性状的关联性，包括单词和非单词阅读流畅性、快速命名、音素删除和非单词重复。在此过程中，我们利用样本的纵向性质来检验这些关联在四个教育时间点（从7岁到12岁）是否稳定。KIAA0319基因中的两个SNP与快速命名名义上相关，并且这些关联在不同年龄都是稳定的。通过使用关于性状发展的纵向信息，可以丰富对复杂认知性状的遗传关联分析。
