The genetic bases of reading and related processes in Russian

描述（由申请人提供）：本项目旨在提高我们的知识和理解的遗传基础的阅读和相关过程。人们早就知道，阅读，无论是作为能力还是残疾，沿着与阅读相关的过程，都是可遗传的，但该领域很难就这种（障碍）能力的特定基因候选人达成一致。该领域已经确定了分子遗传学研究结果缺乏一致性的一些原因。这些原因包括缺乏权力，表型评估的不一致性，以及，也许，对英语的关注，这是世界语言中的一个特殊的离群值。在这个应用程序中，我们试图克服一些以前的研究的局限性，与大样本的俄语兄弟姐妹（n = 400对）和不一致的单例（n = 1,500），其性能的阅读和阅读相关的评估是仔细抽样通过评估电池嵌入在一个特定的理论框架。我们将利用俄罗斯同胞对的全基因组短串联重复多态性（STRP）连锁研究（WGLS）获得的初步结果，并建议使用~4，对来自这2300个个体（同胞对和单例）的DNA上的500个靶向SNP进行基因分型和多变量读数相关表型。所提出的样本、技能和技术的组合提供了一个相当有吸引力的机会，无论是在科学上还是在方法上。该R21将产生试点数据，以（1）建立俄罗斯特定阅读障碍（SRD）儿童的大规模流行病学样本的可行性;（2）调查将同一样本中获得的STRP和SNP数据相结合的可用性;以及（3）估计遗传效应的大小，如果得到证实，并利用更确定和资金需求更高的技术设计后续研究（例如，测序）。 公共卫生相关性：阅读习得和表现方面的困难很常见，在所有研究国家中的患病率为5-7%，无论特定国家的书写系统特征如何。多年来对这些困难的表现和病因的研究已经确定，这是一种终身的状况，对个人来说代价高昂，与失去多年的教育，减少职业成功，以及通常负面的心理健康结果有关。了解阅读困难的病因是至关重要的，为发展适当的方法，其预防和补救。

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.