The genomic bridge project (GBP)

基因组桥计划（GBP）

• 批准号: 8581369
• 负责人: Elise B Robinson
• 金额: $ 15.82万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581369
• 关键词: Address; Adolescence; Affect; Area; Autistic Disorder; Award; Behavior; Behavior Disorders; Behavioral; Behavioral Genetics; Biological Process; Bipolar Disorder; Child; Childhood; Classification; Cognition; Cognitive; DSM-IV; Data; Data Set; Deterioration; Development; Diagnostic and Statistical Manual; Disease; Epidemiologic Methods; Epidemiology; Functional disorder; General Hospitals; General Population; Genes; Genetic; Genetic Crosses; Genetic Variation; Genomics; Genotype; Goals; Impaired cognition; Impairment; Individual; K-Series Research Career Programs; Link; Literature; Longitudinal Studies; Massachusetts; Measures; Mentored Research Scientist Development Award; Mentors; Modeling; Neurodevelopmental Disorder; Outcome; Parents; Pathway interactions; Phenotype; Population; Research; Research Design; Research Project Grants; Research Training; Risk; Sampling; Schizophrenia; Severities; System; Techniques; Testing; Training; Training Technics; Twin Multiple Birth; Twin Studies; Variant; Work; autism spectrum disorder; base; behavior influence; behavioral impairment; career; design; genetic variant; neuropsychiatry; novel; programs; public health relevance; skills; social; symposium; therapeutic target; therapy development; training project; trait

DESCRIPTION (provided by applicant): This Career Development Award (K01) will provide the candidate with the necessary skills to develop an independent research program that uses epidemiologic methods to identify biologically-informative determinants of neuropsychiatric disease. Although current evidence suggests that genetic influences on neuropsychiatric phenotypes cross DSM-IV boundaries, the extent to which either common or rare genetic variants associated with autism, schizophrenia, and bipolar disorder affect behavior and cognition in the general population is not well understood. The overall aim of the current proposal is to test the hypotheses that: 1) there is a genetic link between severely disordered and subclinical behavioral impairments and 2) the genetic variants that increase risk for DSM-IV disorders influence population variation in multiple domains of behavior and cognition. Stated otherwise, this proposal examines the extent to which different types and severities of disordered behavior share genetic influences, or are genomically-bridged. The findings from these studies will help establish sets of behavior that are likely to share underlying pathophysiology. The identification of such etiologically-linked systems of behavior will aid in th classification of individuals for future research studies and accelerate the pace of specifically-targeted treatment development. The training component of the proposed award, centered in the Analytic and Translational Genetics Unit at Massachusetts General Hospital, is designed to provide the candidate with the skills necessary to reach her independent research and career goals, as well as to complete the K01 research aims. Dr. Robinson has a background in behavior genetics (twin studies) and the epidemiology of childhood behavioral disorders, but no training in the use of measured genetic variables or developmental approaches to psychiatric phenotypes. She will accordingly be trained in two novel areas by internationally-recognized experts in each field: 1) statistical genetics, mentored by Dr. Mark Daly, and 2) trajectories of psychiatric neurodevelopmental disorders, mentored by Dr. Ezra Susser. Within these training areas, Dr. Robinson will develop skills in the analysis of both common and rare genetic variation, and integrate those techniques with strategies employed to examine neuropsychiatric phenotypes across the lifecourse. She will be trained in each area through course work; individual training with Drs. Daly, Susser, and seven expert consultants; conference attendance; and supervised research projects. The training aims will be applied in the research component of the award, titled the Genomic Bridge Project: three studies designed by Drs. Robinson, Daly, and Susser to test the hypotheses above. The studies use data from the two largest, individually-genotyped general population datasets in the world in which behavior has been deeply phenotyped from childhood through adolescence, the Twins Early Development Study (TEDS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Together, these training and research projects will constitute the basis for an R01 proposal that Dr. Robinson will prepare in the fourth and fifth years of the award period, under continued guidance from Drs. Daly and Susser. This R01 will employ the training and research completed during the Career Development Award period to investigate the genetic influences on systems of behavioral and cognitive impairment in the general population.

描述（由申请人提供）：该职业发展奖（K01）将为候选人提供必要的技能，以开发独立的研究计划，该计划使用流行病学方法来识别神经精神疾病的生物信息性决定因素。尽管目前的证据表明，遗传对神经精神病表型的影响交叉DSM-IV边界，而与自闭症，精神分裂症和躁郁症相关的常见或稀有遗传变异的程度尚不广泛地了解普通人群中的行为和认知。当前建议的总体目的是检验以下假设：1）严重失调和亚临床行为障碍之间存在遗传联系，而2）增加DSM-IV疾病风险的遗传变异会影响行为和认知的多个领域中人群变异。否则，该提案研究了无序行为的不同类型和严重性具有遗传影响的程度，或者是基因组桥接的。这些研究的发现将有助于建立可能共享潜在病理生理学的行为集。这种与病因相关的行为系统的识别将有助于对个人进行对未来研究的分类，并加快针对特定靶向治疗的发展的节奏。拟议奖的培训部分以马萨诸塞州总医院的分析和转化遗传学部门为中心，旨在为候选人提供实现其独立研究和职业目标所必需的技能，以及完成K01研究的目标。鲁滨逊博士具有行为遗传学（双研究）和儿童行为障碍的流行病学背景，但在使用测量的遗传变量或精神病表型的发育方法方面没有培训。因此，她将在每个领域的国际认可的专家中在两个新的领域进行培训：1）由马克·戴利（Mark Daly）博士指导的统计遗传学，以及2）Ezra Susser博士指导的精神神经发育障碍的轨迹。在这些培训领域，鲁滨逊博士将发展对常见和罕见遗传变异分析的技能，并将这些技术与用于检查整个生命史中的神经精神表型的策略相结合。她将通过课程工作在每个领域接受培训；通过DRS进行个人培训。 Daly，Susser和七位专家顾问；会议出席；和监督研究项目。该培训目标将用于该奖项的研究部分，标题为“基因组桥项目：DRS”设计的三项研究。罗宾逊，戴利和苏瑟测试了上述假设。这些研究使用了世界上两个最大的，单独生成的一般人口数据集的数据，在这些数据集中，从小到青春期，双胞胎早期发展研究（TEDS）和父母和子女的雅芳纵向研究（ALSPAC），对行为进行了深刻的表现。这些培训和研究项目一起将构成R01提案的基础，Robinson博士将 在奖励期的第四和第五年中，在DRS的持续指导下准备。戴利和苏瑟。该R01将采用职业发展奖期间完成的培训和研究，以调查对普通人群行为和认知障碍体系的遗传影响。