Genetic Interactions in Developmental Dyslexia

发育性阅读障碍的遗传相互作用

• 批准号: 7426324
• 负责人: LAUREN M McGRATH
• 金额: $ 1.3万
• 依托单位: UNIVERSITY OF DENVER (COLORADO SEMINARY)
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-14 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7426324
• 关键词: 15q21; 1p36; 2p16; Awareness; Biological; Candidate Disease Gene; Child; Code; Communication; Communication impairment; Complex; Development; Developmental reading disorder; Diagnosis; Disease regression; Dizygotic Twins; Early identification; Emotional; Environment; Etiology; Family; Genes; Genetic; Genetic Models; Genomics; Genotype; Goals; Home environment; Impairment; Intervention; Language; Literature; Mails; Measures; Methods; Modeling; Molecular Genetics; Motivation; Names; Occupational; Orthography; Outcome; Perinatal; Phenotype; Psychopathology; Public Health; Questionnaires; Reading; Reading Disabilities; Recruitment Activity; Schools; Short-Term Memory; Siblings; Testing; Time; Twin Studies; Writing; base; design; developmental disease; falls; follow-up; interest; literacy; phonology; prenatal; psychologic; self esteem; social; spelling; stem; success

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.

描述（由申请人提供）：当前提案的目标是通过关注基因 x 环境相互作用，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能力缺陷，并伴有拼写和解码能力差，所有这些通常源于语言语音成分的潜在弱点。 RD 通常被称为沟通障碍，尤其是在学校环境中，因为它会导致书面语言沟通障碍。 RD 的遗传学已经发展到可以识别候选基因的程度，但这些基因的识别不太可能回答有关 RD 的许多病因学问题，除非考虑到与环境的相互作用。因此，该提案将使用分子遗传学方法和家庭环境以及产前和围产期环境的测量来测试基因 x 环境相互作用。由于测试时仅获得有关家庭环境的有限信息，因此将向家庭邮寄针对家庭识字环境和家庭教育价值观的后续调查问卷。该研究是一项同胞对连锁设计，将利用异卵双胞胎及其亲生兄弟姐妹的基因型和表型，这些兄弟姐妹之前被招募到大型双胞胎研究中。基因型将针对 RD 的 6 个复制连锁区域中的标记：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、言语工作记忆、拼写编码和快速命名的复合表型。将使用这些复合表型来识别 6 个感兴趣的基因组区域中每一个区域的连锁峰。然后，将在这些连锁峰上测试遗传和环境对表型贡献的加性和交互模型。这些分析将实施基于回归的连锁方法的扩展，以测试基因 x 环境相互作用。该项目与公共卫生相关，因为 RD 对学业和职业成功具有影响，并且与自尊、动机和社会情感功能的下降有关。尽管有经过经验验证的治疗方法，但许多儿童直到阅读能力已经落后时才被诊断出来。因此，更好地了解 RD 复杂的遗传和环境原因的研究可以促进早期识别和干预，从而实现更好的学业、心理和职业结果。