Doust Catherine, Gordon Scott D, Garden Natalie, Fisher Simon E, Martin Nicholas G, Bates Timothy C, Luciano Michelle
Department of Psychology, The University of Edinburgh, Edinburgh, Scotland, UK.
Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Twin Res Hum Genet. 2020 Feb;23(1):23-32. doi: 10.1017/thg.2020.7. Epub 2020 Apr 6.
Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7-73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.
阅读和语言能力对教育成就以及成年后的成功至关重要。这些特质的差异具有高度遗传性,但其潜在的遗传结构在很大程度上尚未被发现。传统上,阅读和语言技能的基因研究主要集中在患有发育障碍的儿童身上;然而,现在有大量未经过筛选的成年样本,这增强了识别与小效应量特定基因变体之间关联的能力。我们引入了一个澳大利亚成年人群队列(年龄在41.7 - 73.2岁之间,N = 1505),并使用经过验证的阅读和语言能力多个方面的测量方法获取了数据。我们对阅读和拼写综合得分、非字词阅读(评估语音处理:学习阅读的核心组成部分)、语音拼写、自我报告的阅读障碍以及非字词重复(语言能力的一个指标)进行了基因关联分析。鉴于这样规模的样本中检测力有限(找到最小效应量为0.005时约有80%的检测力),我们专注于分析先前研究中与诵读困难以及发育性言语和语言障碍相关的候选基因。在基于基因的测试中,与言语/语言障碍相关的FOXP2基因与非字词重复(p < 0.001)、语音拼写(p = 0.002)以及阅读和拼写综合得分(p < 0.001)相关。对候选诵读困难和言语/语言障碍基因的基因集分析并不显著。这些发现有助于评估阅读和语言障碍中的基因关联,这对于理解其病因以及为干预策略提供信息至关重要,并且验证了使用未经过筛选的成年样本来发现语言和阅读相关基因的方法。