Luciano Michelle, Gow Alan J, Pattie Alison, Bates Timothy C, Deary Ian J
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland, UK.
Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH9 8JZ, Scotland, UK.
Behav Genet. 2018 Sep;48(5):351-360. doi: 10.1007/s10519-018-9913-3. Epub 2018 Jun 29.
A number of candidate genes for reading and language impairment have been replicated, primarily in samples of children with developmental disability or delay, although these genes are also supported in adolescent population samples. The present study used a systematic approach to test 14 of these candidate genes for association with reading assessed in late adulthood (two cohorts with mean ages of 70 and 79 years). Gene-sets (14 candidates, axon-guidance and neuron migration pathways) and individual SNPs within each gene of interest were tested for association using imputed data referenced to the 1000 genomes European panel. Using the results from the genome-wide association (GWA) meta-analysis of the two cohorts (N = 1217), a competitive gene-set analysis showed that the candidate gene-set was associated with the reading index (p = .016) at a family wise error rate corrected significance level. Neither axon guidance nor neuron migration pathways were significant. Whereas individual SNP associations within CYP19A1, DYX1C1, CNTNAP2 and DIP2A genes (p < .05) did not reach corrected significance their allelic effects were in the same direction as past available reports. These results suggest that reading skill in normal adults shares the same genetic substrate as reading in adolescents, and clinically disordered reading, and highlights the utility of adult samples to increase sample sizes in the genetic study of developmental disorders.
许多与阅读和语言障碍相关的候选基因已得到重复验证,主要是在发育障碍或发育迟缓儿童样本中,不过这些基因在青少年群体样本中也得到了支持。本研究采用系统方法,对其中14个候选基因与成年后期(两个队列的平均年龄分别为70岁和79岁)的阅读能力之间的关联进行了测试。使用参照千人基因组计划欧洲样本的推算数据,对基因集(14个候选基因、轴突导向和神经元迁移途径)以及每个感兴趣基因内的单核苷酸多态性(SNP)进行了关联测试。利用两个队列(N = 1217)的全基因组关联(GWA)荟萃分析结果,竞争性基因集分析表明,在经家族性错误率校正的显著性水平下,候选基因集与阅读指数相关(p = 0.016)。轴突导向途径和神经元迁移途径均无显著性。虽然CYP19A1、DYX1C1、CNTNAP2和DIP2A基因内的个体SNP关联(p < 0.05)未达到校正后的显著性,但其等位基因效应与以往的报告方向相同。这些结果表明,正常成年人的阅读技能与青少年阅读以及临床阅读障碍具有相同的遗传基础,并突出了成年样本在发育障碍基因研究中增加样本量的作用。