Mueller Kathryn L, Murray Jeffrey C, Michaelson Jacob J, Christiansen Morten H, Reilly Sheena, Tomblin J Bruce
Hearing, Language and Literacy, Murdoch Childrens Institute, Melbourne, Australia.
Dept. of Communication Sciences and Disorders, The University of Iowa, Iowa City, United States of America.
PLoS One. 2016 Apr 11;11(4):e0152576. doi: 10.1371/journal.pone.0152576. eCollection 2016.
Much of our current knowledge regarding the association of FOXP2 with speech and language development comes from singleton and small family studies where a small number of rare variants have been identified. However, neither genome-wide nor gene-specific studies have provided evidence that common polymorphisms in the gene contribute to individual differences in language development in the general population. One explanation for this inconsistency is that previous studies have been limited to relatively small samples of individuals with low language abilities, using low density gene coverage. The current study examined the association between common variants in FOXP2 and a quantitative measure of language ability in a population-based cohort of European decent (n = 812). No significant associations were found for a panel of 13 SNPs that covered the coding region of FOXP2 and extended into the promoter region. Power analyses indicated we should have been able to detect a QTL variance of 0.02 for an associated allele with MAF of 0.2 or greater with 80% power. This suggests that, if a common variant associated with language ability in this gene does exist, it is likely of small effect. Our findings lead us to conclude that while genetic variants in FOXP2 may be significant for rare forms of language impairment, they do not contribute appreciably to individual variation in the normal range as found in the general population.
我们目前关于FOXP2与言语和语言发育之间关联的许多知识来自于单病例和小家族研究,这些研究中已鉴定出少量罕见变异。然而,全基因组研究和基因特异性研究均未提供证据表明该基因中的常见多态性会导致普通人群语言发育的个体差异。对于这种不一致的一种解释是,先前的研究仅限于语言能力较低的相对小样本个体,且基因覆盖密度较低。本研究在一个基于人群的欧洲裔队列(n = 812)中,检测了FOXP2常见变异与语言能力定量指标之间的关联。对于一组覆盖FOXP2编码区并延伸至启动子区的13个单核苷酸多态性(SNP),未发现显著关联。效能分析表明,对于等位基因频率(MAF)为0.2或更高的相关等位基因,我们应有80%的效能检测到0.02的数量性状位点(QTL)变异。这表明,如果该基因中确实存在与语言能力相关的常见变异,其效应可能较小。我们的研究结果使我们得出结论,虽然FOXP2中的遗传变异可能对罕见形式的语言障碍具有重要意义,但它们对普通人群中正常范围内的个体差异贡献不大。