Details of Genomewide Association Results, Protocol, Statistical Analysis, and Additional References (Harlaar et al., 2014)

Purpose Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association approach.

Method The authors administered 4 Internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2,329 twelve-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and 1 million imputed SNPs were included in a genome-wide association analysis of receptive language composite scores.

Results No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome ( p < 5 × 10−8). The strongest SNP association did not replicate in an additional sample of 2,639 twelve-year-olds.

Conclusions These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for more than 3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants.

研究目的：先前研究表明，12岁儿童在接受性语言能力测量上的个体差异具有高度的可遗传性。在当前研究中，作者试图通过全基因组关联方法，确定一些负责接受性语言能力可遗传性的基因。研究方法：作者对2,329名具有DNA和全基因组基因分型的12岁儿童进行了4项基于互联网的接受性语言能力测量（词汇、语义、句法和语用学）。在全基因组关联分析中，纳入了近70万个单核苷酸多态性（SNPs）和100万个推断的SNPs，以分析接受性语言综合评分。研究结果：没有SNPs关联达到全基因组显著性水平（校正基因组多重检验的p值<5×10−8）。最强的SNPs关联在额外的2,639名12岁儿童的样本中没有得到复制。研究结论：这些结果表明，在普通人群中，接受性语言能力的个体差异并不反映能够解释超过3%表型变异的常见遗传变异。寻找与语言技能相关的遗传变异需要更大的样本量和额外的识别及功能表征风险变异全谱系的方法。