Integrated gene and brain mapping of language and reading abilities

使用语言进行交流的能力是人类独有的。语言是我们社交世界的中心，相关的阅读和写作技能是教育和日常生活的中心。人们对语言的理解和使用程度不同，阅读和写作能力也不同，我们的研究旨在更好地了解普通人群语言和阅读能力个体差异背后的生物学。这一领域的大多数遗传学研究都集中在学习语言和阅读技能有困难的儿童身上，但这些样本量太小，无法找到可能影响这些特征正常变异的非常小的个体效应的共同基因。我们的研究是新颖的，因为它收集了成年人的语言和阅读测量，因此可以迅速获得足够大的样本量来进行基因发现。我们关注的样本是特殊的，主要有三个原因。1)他们已经有了全基因组的基因分型数据，所以一旦在这个样本中测量了语言和阅读能力，我们就可以进行我们的基因发现分析(基因组范围关联；GWA)。2)最近，一组样本接受了磁共振成像(MRI)的大脑扫描，这样我们就可以调查他们的语言和阅读技能与大脑的结构特征和网络结构之间的关系。重要的是，这些样本中的一些人有儿童(7-11岁)阅读技能的历史测量，这样我们就可以测试他们的童年阅读成绩是否与成年时测量的相同大脑结构和网络有关。3)样本有全基因组甲基化数据。甲基化是一种可以与DNA结合、影响基因表达和改变基因功能的化学标记。这种表观遗传(对基因表达的非遗传影响)标记以前没有被测试过它与语言和阅读技能的关联，我们的研究将提供这方面的第一次调查。我们的GWA结果将与国际GWA队列的结果相结合，产生最大的GWA语言和阅读能力。我们可以通过在带有语言/阅读测量的多变量GWA荟萃分析中使用脑MRI标记来进一步提高基因发现的能力。最后，我们将对基因表达、甲基化和遗传数据进行综合分析，以进一步发现与语言和阅读能力相关的新基因，并更好地了解基因外变体的作用。我们将遗传学、表观遗传学和脑成像研究流结合在一起的新方法将为理解语言和阅读能力的生物学提供一个全面的框架，使从基因到大脑再到行为的重要联系成为可能。

The ability to communicate using language is unique to humans. Language is central to our social world, and associated reading and writing skills are central to education and daily life. People vary in how well they comprehend and use language, and in their abilities to read and write, our research aims to better understand the biology behind these individual differences in language and reading abilities in the general population. Most genetic research in this area has focussed on children who have difficulties acquiring language and reading skills, but these sample sizes are too small to find the common genes of very small individual effect that are likely to influence normal variation in these traits. Our research is novel because it collects language and reading measures in adults, and can therefore rapidly attain sample sizes large enough to make genetic discoveries. The sample that we focus on is special for three main reasons. 1) They already have genome-wide genotyping data available, so we can run our gene discovery analysis (genome-wide association; GWA) as soon as language and reading skills have been measured in this sample. 2) A subsample have recently had their brain scanned using magnetic resonance imaging (MRI), so we can investigate how their language and reading skills relate to structural features and networks of the brain. Importantly, some of this sample have historical measures of reading skill in childhood (7-11 years), so that we can test whether their childhood reading scores are related to the same brain structures and networks measured in adulthood. 3) The sample have genome-wide methylation data available. Methylation is a chemical mark that can attach to DNA and affect gene expression and modify gene function. This type of epigenetic (non-genetic influence on gene expression) marker has not previously been tested for its association with language and reading skills, our study will provide the first investigation of this. Our GWA results will be combined with those from international GWA cohorts to produce the largest GWA of language and reading abilities. We can further boost power of gene discovery by using brain MRI markers in a multivariate GWA meta-analysis with language/reading measures. Finally, we will perform an integrated analysis of gene expression, methylation, and genetic data to find further novel genes associated with language and reading abilities, and to better understand the role of variants that lie outside genes. Our novel approach of combining genetic, epigenetic, and brain imaging research streams will provide a comprehensive framework for understanding the biology of language and reading abilities, enabling the important link from genes to brain to behaviour.