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与环境的相互作用，更好地了解发育性阅读障碍或阅读障碍（RD）的复杂多因素病因。口吃障碍的定义是缺乏流利的单词识别能力，并伴有拼写和解码能力差，所有这些通常都源于语言语音成分的潜在弱点。自闭症通常被认为是一种沟通障碍，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确定候选基因的地步，但这些基因的鉴定不太可能回答许多关于RD的病因学问题，除非考虑到与环境的相互作用。因此，本提案将使用分子遗传学方法和家庭环境、产前和围产期环境的测量来测试基因x环境的相互作用。由于测试时所获得的家庭环境信息有限，因此我们将邮寄针对家庭文化环境和家庭教育价值的后续问卷给这些家庭。这项研究是一个兄弟姐妹连锁设计，将利用来自异卵双胞胎及其生物学兄弟姐妹的基因型和表型，这些兄弟姐妹之前被招募到一项大型双胞胎研究中。这些基因型将针对6个RD复制连锁区域的标记：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、正字法编码和快速命名的复合表型。将利用这些复合表型确定6个感兴趣的基因组区域中的每一个的连锁峰。然后，将在这些连锁峰上测试遗传和环境对表型贡献的加性和相互作用模型。分析将实现基于回归的连锁方法的扩展，以测试基因与环境的相互作用。该项目与公共卫生相关，因为RD对学术和职业成功有影响，并与自尊、动机和社会情感功能的下降有关。虽然有经验验证的治疗方法，但许多儿童直到阅读能力已经落后才被诊断出来。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，从而获得更好的学术、心理和职业结果。