The genetic bases of reading and related processes in Russian

描述(由申请者提供)：本项目旨在提高我们对阅读和相关过程的遗传学基础的认识和理解。人们早就知道，阅读，无论是能力还是残疾，以及与阅读相关的过程都是可遗传的，但这个领域很难集中到这种(非)能力的特定基因候选上。该领域已经确定了分子遗传学发现之间缺乏趋同的一些原因。这些原因包括缺乏力量，表型评估的不一致，也许是对英语的关注，这在世界语言中是一个特别的异常值。在这项研究中，我们试图克服以前研究的一些局限性，方法是使用大样本的讲俄语的兄弟姐妹(n=400对)和不同的单身人士(n=1500)，他们在阅读和与阅读相关的评估上的表现是通过嵌入特定理论框架的评估单元仔细抽样的。我们将利用通过俄罗斯同胞对的全基因组短串联重复-重复-多态(STRP)连锁研究(WGLS)获得的初步结果，并建议使用这2300个个体(同胞对和单态)DNA上的~4,500个目标SNP和多变量阅读相关表型，完成基于单核苷酸多态(SNP)的WGLS中确定的感兴趣区域的调查。提出的样本、技能和技术的组合提供了一个相当吸引人的机会，无论是在科学上还是在方法上。R21将产生试点数据，以(1)确定构建俄罗斯特定阅读障碍(SRD)儿童的大流行病学样本的可行性；(2)调查结合在同一样本上获得的STRP和SNP数据的可用性；以及(3)估计基因效应的大小，如果得到证实，并利用更明确和更需要资金的技术(如测序)设计后续研究。 与公共健康相关：在所有被研究的国家中，无论特定国家的书写系统的特点如何，阅读习得和表现方面的困难都很常见，而且普遍存在5%至7%的情况。多年来对这些困难的表现和病因的研究已经确定，这是一种终生疾病，对个人来说代价高昂，与失去多年教育、事业成功减少以及往往是负面的心理健康结果有关。了解阅读困难的病因对于制定适当的预防和补救方法至关重要。

DESCRIPTION (provided by applicant): This project is aimed at enhancing our knowledge and understanding of the genetic bases of reading and related processes. It has long been known that reading, whether qualified as ability or disabilities, along with reading-related processes, are heritable, but it has been rather difficult for the field to converge on specific gene candidates for this (dis)ability. The field has identified a number of reasons for such a lack of convergence among the molecular-genetic findings. These reasons include lack of power, inconsistencies in phenotypic evaluations, and, perhaps, the focus on English, which is a particular outlier among world languages. In this application, we attempt to overcome some of the limitations of previous studies by working with large samples of Russian-speaking siblings (n = 400 pairs) and discrepant singletons (n = 1,500), whose performance on reading and reading-related assessments is carefully sampled through an assessment battery embedded in a particular theoretical framework. We will capitalize on preliminary findings obtained through a whole-genome short-tandem-repeat-polymorphism (STRP) linkage study (WGLS) of Russian sib pairs and propose to complete a single-nucleotide-polymorphism (SNP)-based investigation of the regions of interest identified in the WGLS using ~4,500 targeted SNPs genotyped on the DNA from these 2300 individuals (sib pairs and singletons) and multivariate reading-related phenotypes. The proposed combination of samples, skills, and technologies provides a rather appealing opportunity, both scientifically and methodologically. This R21 will generate pilot data to (1) establish the feasibility of constructing a large epidemiologically-based sample of Russian children with specific reading disability (SRD); (2) investigate the usability of combining STRP and SNP data obtained on the same sample; and (3) estimate the sizes of genetic effects, if confirmed, and design subsequent studies utilizing more definitive and funding-demanding technologies (e.g., sequencing). PUBLIC HEALTH RELEVANCE: Difficulties in reading acquisition and performance are common and observed at the prevalence of 5-7% in all studied countries, regardless of the characteristics of the writing system within a given country. Years of research into the manifestation and etiology of these difficulties have established that it is a life-long condition unfolding at high cost to an individual, associated with lost years of education, diminished career success, and often negative mental health outcomes. Understanding the etiology of reading difficulties is crucial for developing adequate methods for its prevention and remediation.