Molecular genetics of executive function in dyslexia

描述（由申请人提供）：此培训资助的目的是帮助申请人在精神病学和行为遗传学领域建立独立的研究生涯。该候选人已完成精神病学和儿童精神病学的临床培训，并在简单孟德尔和基因组疾病的分子遗传学方面具有先前的研究经验。候选人的培训将在华盛顿大学温蒂·拉斯金德博士的实验室进行。拉斯金德博士是一个研究阅读障碍的成熟多学科研究小组的成员。本研究旨在探讨阅读障碍的遗传基础。阅读障碍是一种常见而复杂的疾病，遗传因素在其中起着重要的作用。语音加工和潜在的语言加工受损已被确定为阅读障碍的核心缺陷。近年来，注意力和执行功能因素的作用越来越被认识到。注意和执行功能缺陷通常在许多遗传性精神疾病中观察到。阅读障碍也与儿童时期的精神疾病如多动症有显著的共病性。研究注意力和执行功能的遗传基础可能有助于阐明其他精神疾病的遗传基础。尽管由于诊断标准和遗传异质性缺乏共识，阅读障碍的遗传研究可能会变得复杂，但本研究将采用复杂的表型评估和统计分析方法来克服这些并发症，并确定导致这种复杂行为表型的基因。为了阐明阅读障碍的遗传基础，申请人建议：

Description (provided by the applicant): The purpose of this training grant is to help establish the candidate's independent research career in the field of psychiatric and behavioral genetics. The candidate has completed clinical training in psychiatry and child psychiatry, and has prior research experience in molecular genetics of simple Mendelian and genomic disorders. The candidate's training will take place in the laboratory of Dr. Wendy Raskind at the University of Washington. Dr. Raskind is part of an established multidisciplinary research team investigating dyslexia. This study proposes to investigate the genetic basis for dyslexia. Dyslexia is a common and complex disorder in which genetics has a significant component. Impaired phonological processing and underlying language processes have been identified as core deficits in dyslexia. Recently, the contributions of attention and executive functioning factors have been increasingly recognized. Attention and executive function deficits are commonly observed in many heritable psychiatric disorders. Dyslexia also demonstrates significant comorbidity with psychiatric disorders of childhood such as ADHD. Studying the genetic basis of attention and executive functioning may help elucidate the genetic underpinnings of additional psychiatric disorders. Although genetic studies of dyslexia can be complicated by a lack of consensus on diagnostic criteria and by genetic heterogeneity, this study will employ sophisticated phenotype assessment and statistical analysis methodologies to overcome these complications and in order to identify genes that contribute to this complex behavioral phenotype. To elucidate the genetic basis of dyslexia, the applicant proposes to: (1) To evaluate attention and executive function component phenotypes for suitability for genetic studies. (2) To localize genes that contribute to performance on quantitative measures of attention and executive function by genome-wide linkage analyses (3) To evaluate candidate genes which are implicated in attention networks for association with the identified component phenotypes of dyslexia (4) To refine the genetic loci identified in Specific Aim (2) The candidate's immediate career goal is to acquire the necessary skills to study complex genetic disorders. This training grant will allow the candidate to build upon his prior experiences in the molecular genetics of "simple" Mendelian disorders and afford the applicant the opportunities to (1) learn methods for understanding and dissecting complex cognitive/behavioral phenotypes, (2) acquire new molecular genetics skills pertinent to common genetic variations and complex phenotypes, and (3) attain new statistical genetics skills relevant to the study of complex genetics. These goals will be accomplished through formal didactic coursework and practical performance of laboratory, linkage and association studies. The candidate's longterm career goal is to study the etiology of complex psychiatric disorders that have varying degrees of genetic influences.