Exploring neural markers of dyslexia as candidate endophenotypes

描述（由申请人提供）：发展性阅读障碍具有高度遗传性，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，使用神经影像学发现的阅读障碍的神经标记可能是内表型：肉眼看不到的与阅读障碍相关的中间性状，但与潜在的基因型更直接相关。我们建议：(1)探索阅读障碍的神经标记因素（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型之间的关系（目标3）。我们希望找到与行为表型和潜在基因型相关的神经因素。这样的一个标记将是一个有希望的候选内表型，可以使寻找易感基因更直接，反过来可能导致未来对阅读障碍的新的生物治疗。

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.