Scerri T S, Macpherson E, Martinelli A, Wa W C, Monaco A P, Stein J, Zheng M, Suk-Han Ho C, McBride C, Snowling M, Hulme C, Hayiou-Thomas M E, Waye M M Y, Talcott J B, Paracchini S
Walter and Eliza Hall Institute of Medical Research & Melbourne University, Parkville, VIC, Australia.
School of Medicine, University of St Andrews, St Andrews, UK.
Transl Psychiatry. 2017 Jul 25;7(7):e1182. doi: 10.1038/tp.2017.151.
Dyslexia is a specific impairment in learning to read and has strong heritability. An intronic deletion within the DCDC2 gene, with ~8% frequency in European populations, is increasingly used as a marker for dyslexia in neuroimaging and behavioral studies. At a mechanistic level, this deletion has been proposed to influence sensory processing capacity, and in particular sensitivity to visual coherent motion. Our re-assessment of the literature, however, did not reveal strong support for a role of this specific deletion in dyslexia. We also analyzed data from five distinct cohorts, enriched for individuals with dyslexia, and did not identify any signal indicative of associations for the DCDC2 deletion with reading-related measures, including in a combined sample analysis (N=526). We believe we conducted the first replication analysis for a proposed deletion effect on visual motion perception and found no association (N=445 siblings). We also report that the DCDC2 deletion has a frequency of 37.6% in a cohort representative of the general population recruited in Hong Kong (N=220). This figure, together with a lack of association between the deletion and reading abilities in this cohort, indicates the low likelihood of a direct deletion effect on reading skills. Therefore, on the basis of multiple strands of evidence, we conclude that the DCDC2 deletion is not a strong risk factor for dyslexia. Our analyses and literature re-evaluation are important for interpreting current developments within multidisciplinary studies of dyslexia and, more generally, contribute to current discussions about the importance of reproducibility in science.
阅读障碍是一种在学习阅读方面的特定障碍,具有很强的遗传性。DCDC2基因内的一个内含子缺失在欧洲人群中的频率约为8%,在神经影像学和行为研究中越来越多地被用作阅读障碍的标志物。在机制层面上,有人提出这种缺失会影响感觉处理能力,尤其是对视觉连贯运动的敏感性。然而,我们对文献的重新评估并未发现有力证据支持这一特定缺失在阅读障碍中起作用。我们还分析了来自五个不同队列的数据,这些队列中阅读障碍个体富集,但未发现任何表明DCDC2缺失与阅读相关指标存在关联的信号,包括在合并样本分析中(N = 526)。我们认为我们首次对提出的缺失对视觉运动感知的影响进行了重复分析,未发现关联(N = 445对兄弟姐妹)。我们还报告说,在香港招募的代表一般人群的一个队列中(N = 220),DCDC2缺失的频率为37.6%。这个数字,连同该队列中缺失与阅读能力之间缺乏关联,表明该缺失对阅读技能产生直接影响的可能性很低。因此,基于多方面的证据,我们得出结论,DCDC2缺失不是阅读障碍的一个强大风险因素。我们的分析和文献重新评估对于解释阅读障碍多学科研究中的当前进展很重要,更广泛地说,有助于当前关于科学中可重复性重要性的讨论。