Exploring neural markers of dyslexia as candidate endophenotypes

探索阅读障碍的神经标志物作为候选内表型

• 批准号: 7869939
• 负责人: Thad A Polk
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7869939
• 关键词: Accounting; Affect; Alleles; Behavior; Behavioral; Biological; Brain; Candidate Disease Gene; Chromosomes, Human, Pair 6; Cognitive; Complex; Developmental reading disorder; Diffusion Magnetic Resonance Imaging; Disease; Dyslexia; Epigenetic Process; Eye; Factor Analysis; Functional Magnetic Resonance Imaging; Future; Genes; Genetic Risk; Genotype; Goals; Impairment; Lead; Learning; Learning Disabilities; Left; Light; Link; Magnetic Resonance Imaging; Measurable; Measures; Participant; Pathway interactions; Performance; Phenotype; Process; Reading; Research; Risk; Schizophrenia; School-Age Population; Screening procedure; Single Nucleotide Polymorphism; Structure; Susceptibility Gene; Symptoms; Variant; Work; base; behavioral impairment; endophenotype; genetic analysis; genome wide association study; genome-wide analysis; improved; interest; lexical; magnocellular; neuroimaging; novel; phonology; public health relevance; relating to nervous system; response; spelling; trait

DESCRIPTION (provided by applicant): Developmental dyslexia is highly heritable, but the search for susceptibility genes is challenging because the pathway from genotype to dyslexic phenotypes is very complex. We hypothesize that neural markers of dyslexia that have been discovered using neuroimaging could be endophenotypes: intermediate traits unseen by the unaided eye that are associated with dyslexia but that are more directly linked to the underlying genotype. We propose to (1) explore the factors underlying neural markers of dyslexia (Aim 1), (2) explore the relationship between the neural factors and behavior (Aim 2) and (3) explore the relationship between the neural factors and a specific genotype that is associated with dyslexia risk (Aim 3). We hope to find a neural factor that is associated with both a behavioral phenotype and an underlying genotype. Such a marker would be a promising candidate endophenotype that could make the search for susceptibility genes more straightforward, and in turn could lead to novel biological treatments for dyslexia in the future. PUBLIC HEALTH RELEVANCE: Identifying the genes that contribute to dyslexia could revolutionize treatment, but is very challenging. We plan to search for a neural signature of dyslexia that is on the pathway from genes to the behavioral impairments in the hopes of making the search for dyslexia genes more straightforward and successful.

描述(申请人提供)：发育性阅读障碍具有高度的遗传性，但寻找易感基因具有挑战性，因为从基因型到阅读障碍表型的途径非常复杂。我们假设，使用神经成像发现的诵读困难的神经标记可能是内表型：肉眼看不到的中间特征，与诵读困难有关，但与潜在的基因更直接相关。我们建议(1)探索阅读障碍神经标志物的潜在因素(目标1)，(2)探索神经因素与行为之间的关系(目标2)，(3)探索神经因素与与阅读障碍风险相关的特定基因之间的关系(目标3)。我们希望找到一种神经因素，既与行为表型相关，又与潜在的基因相关。这样的标记将是一个很有希望的候选内表型，可以使寻找易感基因变得更加直接，进而可能在未来导致新的阅读障碍的生物治疗方法。 与公共卫生相关：识别导致阅读障碍的基因可能会给治疗带来革命性的变化，但这是非常具有挑战性的。我们计划寻找阅读障碍的神经标志，它位于从基因到行为障碍的途径上，希望使对阅读障碍基因的搜索更加直接和成功。