Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
BMC Neurosci. 2020 Jul 7;21(1):30. doi: 10.1186/s12868-020-00581-5.
One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects.
Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis.
Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.
语言是人类最基本的特征之一。在家庭和双胞胎研究中，语言能力和障碍都显示出很强的遗传成分，但相对于其他认知特征和神经发育特征的研究，语言表型的分子遗传学研究还很少。此外，大多数研究这些表型的遗传研究都没有纳入母源效应，而母源效应可能是所研究特征遗传的一部分。我们对接受性语言进行了全基因组关联研究，同时检查了儿童遗传效应和母源效应。
我们使用了一个基于家庭的队列，其中有 400 名儿童的接受性语言评分，我们发现了一个在染色体 9q21.31 上的 SNP rs11787922 的全基因组显著的父源母源效应，T 等位基因使平均接受性语言评分降低了约 23，这相当于超过人口 SD 的 1.5 倍（P=1.04×10）。我们进一步通过纳入儿童的更广泛的神经发育诊断和家庭精神诊断病史的协变量，并重复分析，证实了这种关联不是由这些因素驱动的。
我们的研究报告了一个全基因组显著的与接受性语言技能相关的关联；据我们所知，这是该表型首次被记录的全基因组显著关联。此外，我们的研究说明了在关联研究中考虑母源效应的重要性，特别是在认知或神经发育特征的情况下，其中并不总是纳入父母的遗传数据。
