CNTNAP2 variants affect early language development in the general population.
CNTNAP2 variants affect early language development in the general population.
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DOI：
10.1111/j.1601-183x.2011.00684.x
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发表时间：
2011-06
期刊：
影响因子：
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通讯作者：
Fisher SE
中科院分区：
文献类型：
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作者：
Whitehouse AJ;Bishop DV;Ang QW;Pennell CE;Fisher SE
早期的语言发展被认为受到基因的影响，但影响普通人群正常变异的基因在很大程度上仍然难以捉摸。最近的疾病研究报告说，CNTNAP 2基因的变体与特定语言障碍（SLI）的语言缺陷和自闭症的语言延迟有关。我们测试的假设，这些CNTNAP 2变异影响交际行为，在2岁的大流行病学样本，西澳大利亚州怀孕队列（雷恩）研究。对1149名儿童（606名男性和543名女性）进行的单点分析显示，这些关联模式与以前对语言障碍的研究中观察到的模式惊人地相似，集中在相同的遗传标记上，并且具有一致的效应方向（rs 2710102，P = 0.0239; rs759178，P = 0.0248）。基于这些发现，我们对rs 2710102-rs759178-rs 17236239-rs 2538976四种标记单倍型进行了分析，并确定了显著的相关性（单倍型TTAA，P = 0.049;单倍型GCAG，P = 0.0014）。我们的研究表明，CNTNAP 2外显子13-15区域的常见变异影响了一般人群2岁时的早期语言习得。我们认为，这些CNTNAP 2变异增加了SLI或自闭症的易感性，当它们与其他危险因素一起发生时。
Early language development is known to be under genetic influence, but the genes affecting normal variation in the general population remain largely elusive. Recent studies of disorder reported that variants of the CNTNAP2 gene are associated both with language deficits in specific language impairment (SLI) and with language delays in autism. We tested the hypothesis that these CNTNAP2 variants affect communicative behavior, measured at 2 years of age in a large epidemiological sample, the Western Australian Pregnancy Cohort (Raine) Study. Singlepoint analyses of 1149 children (606 males and 543 females) revealed patterns of association which were strikingly reminiscent of those observed in previous investigations of impaired language, centered on the same genetic markers and with a consistent direction of effect (rs2710102, P = 0.0239; rs759178, P = 0.0248). On the basis of these findings, we performed analyses of four-marker haplotypes of rs2710102–rs759178–rs17236239–rs2538976 and identified significant association (haplotype TTAA, P = 0.049; haplotype GCAG, P = .0014). Our study suggests that common variants in the exon 13–15 region of CNTNAP2 influence early language acquisition, as assessed at age 2, in the general population. We propose that these CNTNAP2 variants increase susceptibility to SLI or autism when they occur together with other risk factors.