Genetic Interactions in Developmental Dyslexia

描述(由申请人提供)：当前提案的目标是通过关注基因与环境的相互作用，更好地理解发育性阅读障碍或阅读障碍(RD)的复杂多因素病因。RD的定义是流利的单词识别缺陷，伴随着糟糕的拼写和解码能力，所有这些都典型地源于语言的语音成分的潜在弱点。RD通常被称为一种交流障碍，尤其是在学校环境中，因为它会导致书面语言交流的障碍。RD的遗传学已经发展到了识别候选基因的地步，但除非考虑到与环境的相互作用，否则这些基因的识别不太可能回答许多关于RD的病因学问题。因此，这项提议将使用家庭环境以及产前和围产期环境的分子遗传学方法和测量来测试基因x环境的相互作用。由于在测试时获得的关于家庭环境的信息有限，后续针对家庭识字环境和家庭教育价值的问卷将邮寄给家庭。这项研究是一项同胞对连锁设计，它将利用先前被招募到大型双胞胎研究中的异卵双胞胎及其亲生兄弟姐妹的基因类型和表型。这些基因将针对RD的6个重复连锁区域中的标记：1p36-p34、2p16-p15、3p12-q13、6p22.2、15q21和18p11.2。将构建评估单词识别、语音解码、语音意识、文字工作记忆、拼写编码和快速命名的复合表型。使用这些复合表型将识别6个感兴趣的基因组区域中的每一个的连锁峰。然后，将在这些连锁峰测试遗传和环境对表型贡献的相加和交互模型。这些分析将实现基于回归的连锁方法的扩展，以测试基因x环境的交互作用。这个项目与公共健康相关，因为研发对学业和职业成功有影响，它与自尊、动机和社会情绪功能的下降有关。虽然有经验验证的治疗方法可用，但许多儿童直到他们在阅读方面落后才被诊断出来。因此，更好地了解RD的复杂遗传和环境原因的研究可以促进早期识别和干预，从而实现更好的学术、心理和职业结果。

DESCRIPTION (provided by applicant): The goal of the current proposal is to better understand the complex multifactorial etiology of developmental dyslexia, or reading disability (RD), by focusing on gene x environment interactions. RD is defined by deficits in fluent word recognition that are accompanied by poor spelling and decoding abilities, all of which typically stem from underlying weaknesses in the phonological component of language. RD is often referred to as a communication disorder, especially in school settings, because it causes impairments in written language communication. The genetics of RD has advanced to the point of identifying candidate genes, but the identification of these genes is unlikely to answer many of the etiological questions about RD, unless interactions with the environment are considered. As such, this proposal will test for gene x environment interactions using molecular genetic methods and measures of the home environment and the prenatal and perinatal environment. Because only limited information about the home environment was obtained at the time of testing, follow-up questionnaires targeting the home literacy environment and family educational values will be mailed to the families. The study is a sib-pair linkage design that will utilize genotypes and phenotypes from dizygotic twins and their biological siblings who were previously recruited into a large twin study. The genotypes will target markers in 6 of the replicated linkage regions for RD: 1p36-p34, 2p16-p15, 3p12-q13, 6p22.2, 15q21,and 18p11.2. Composite phenotypes assessing word recognition, phonological decoding, phonological awareness, verbal working memory, orthographic coding, and rapid naming will be constructed. Linkage peaks in each of the 6 genomic regions of interest will be identified using these composite phenotypes. Then, additive and interactive models of genetic and environmental contributions to the phenotypes will be tested at these linkage peaks. The analyses will implement extensions of regression-based linkage methods in order to test for gene x environment interactions. This project has relevance for public health because RD has implications for academic and occupational success and it is associated with decreases in self-esteem, motivation, and social-emotional functioning. Although there are empirically-validated treatments available, many children are not diagnosed until they have already fallen behind in reading. Thus, studies to better understand the complex genetic and environmental causes of RD could facilitate early identification and intervention enabling better academic, psychological, and occupational outcomes.