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。语言是我们社会的核心，相关的阅读和写作技能是教育和日常生活的核心。人们在理解和使用语言的能力以及阅读和写作能力方面各不相同，我们的研究旨在更好地了解普通人群中语言和阅读能力个体差异背后的生物学。这一领域的大多数基因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化的非常小的个体影响的共同基因。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。我们关注的样本之所以特别，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，所以我们可以运行我们的基因发现分析（全基因组关联；GWA）一旦在这个样本中测量了语言和阅读能力。2)我们最近用核磁共振成像（MRI）扫描了一个子样本的大脑，这样我们就可以研究他们的语言和阅读技能与大脑的结构特征和网络之间的关系。重要的是，这些样本中的一些人在童年（7-11岁）有阅读技能的历史测量，因此我们可以测试他们童年的阅读分数是否与成年时测量的相同的大脑结构和网络有关。3)样本具有全基因组甲基化数据。甲基化是一种可以附着在DNA上影响基因表达和修饰基因功能的化学标记。这种类型的表观遗传（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系，我们的研究将提供这方面的第一次调查。我们的GWA结果将与来自国际GWA队列的结果相结合，以产生最大的GWA语言和阅读能力。我们可以通过在多变量GWA荟萃分析中使用脑MRI标记物与语言/阅读测量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，并更好地理解基因外变异的作用。我们将遗传学、表观遗传学和脑成像研究相结合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，使基因、大脑和行为之间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.