Amish Connectome Project on Mental Illness

阿米什精神疾病连接组项目

• 批准号: 9139980
• 负责人: L Elliot Elliot Hong
• 金额: $ 99.81万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-10 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9139980
• 关键词: Adult; Affect; Alcohol or Other Drugs use; Alleles; Amish; Anisotropy; Attention; Back; Behavior; Behavior assessment; Behavioral; Big Data; Brain; CNTNAP1 gene; Cerebrum; Characteristics; Clinic; Clinical; Cognition; Collection; Communities; Data; Data Collection; Databases; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Economics; Educational Background; Family; Family Sizes; Feasibility Studies; Frequencies; Fright; General Population; Generations; Genes; Genetic; Genetic Structures; Genetic study; Glossary; Goals; Health; Health Services Research; High Prevalence; Human; Illicit Drugs; Image; Individual; Inheritance Patterns; Inherited; Interview; Lead; Life; Light; Longevity; Major Depressive Disorder; Measures; Medical Genetics; Mental disorders; Meta-Analysis; Methods; Nature; Nuclear Family; Participant; Pathway interactions; Perfusion; Phenotype; Play; Population; Privacy; Protocols documentation; Psychiatric Diagnosis; Rare Diseases; Recording of previous events; Recruitment Activity; Research; Research Design; Research Domain Criteria; Research Infrastructure; Research Personnel; Rewards; SNP array; Sampling; Short-Term Memory; Social Welfare; Socioeconomic Status; Structure; Symptoms; System; Test Result; Testing; Translating; United States National Institutes of Health; Voltage-Gated Potassium Channel; Work; base; brain circuitry; clinical practice; cohort; connectome; data sharing; database of Genotypes and Phenotypes; design; distributed data; endophenotype; genetic analysis; genetic linkage; genetic linkage analysis; genetic risk factor; genetic variant; genome sequencing; genome wide association study; genomic data; human disease; identity by descent; imaging genetics; indexing; insight; interest; member; mental disorder diagnosis; neuroimaging; neuropsychological; next generation sequencing; processing speed; programs; rare variant; relating to nervous system; risk variant; success; trait; transmission process; whole genome; willingness

 DESCRIPTION (provided by applicant): The Amish Connectome Project (ACP) will extend the Human Connectome Project (HCP) to mental illnesses by characterizing brain circuitry and its relation to psychiatric behavior and symptom dimensions. We propose to collect HCP connectomics and whole genome sequencing data in Old Order Amish (OOA) adults recruited from multigenerational families with multiplex mental disorders spanning diagnostic boundaries. Large nuclear families with two or more members with major DSM-5 disorder will be recruited for phenotyping using the full HCP lifespan imaging and behavioral protocol expanded to Research Domain Criteria (RDoC) standard. The advent of non-invasive connectivity-oriented neuroimaging methods has shed new light onto the inner workings of the brain. The brain's functional and structural connectome plays key roles in regulating the pathway from genes to neural systems to mental illnesses. Extending the gene -->connectome HCP approach to gene -->connectome -->mental disorder in HCP-Human Disease adds tremendous opportunity to identify genetic underpinning of heritable mental disorders. ACP offers a uniquely efficient and powerful study design that is critical for a successful breakthrough. The ACP will study large, multigenerational families from a population isolate, which is a powerful statistical design for discovery of genetic linkage between connectomic traits and mental disorders. The OOA sample is unique in its relative genetic uniformity, with ancestry recorded in the NIH database and traceable back fourteen generations to limited founders. This sample is also unique because of its relative uniformity in educational background, life and work conditions, socioeconomic status and much reduced influence by illicit drugs. These unique characteristics of OOA community members, combined with their large family size, makes the OOA a powerful population sample to study the genetic factors that alter cerebral connectivity in mental disorders with familial pattern of inheritance. We will expand upon HCP protocol with the psychiatric diagnosis, broad symptom and RDoC dimensional assessments of behavior and cognition. Whole genome data will be obtained for all participants through next generation sequencing and family-based imputation of GWAS data. These data will be shared with the large research community while protecting the privacy, confidentiality and welfare of participants, with special attention given to protect the welfare of the OOA community. Medical genetic discoveries in OOA have routinely been replicated in general population samples and translated to clinical practice. We are inspired to create opportunities to allow repetitions of suh success in brain connectome and in mental illness through shared data effort, and have assembled an efficient team to lead this endeavor.

 描述（由应用程序提供）：Amish ConnectMe项目（ACP）将通过表征脑电路及其与精神病行为和症状维度的关系，将人类连接项目（HCP）扩展到精神疾病。我们建议以旧顺序Amish（OOA）的成年人从具有多种精神疾病的多元基质家庭招募的旧顺序Amish（OOA）成年人收集HCP连接组学和整个基因组测序数据。将使用全HCP寿命成像和行为方案扩展到研究领域标准（RDOC）标准的全HCP寿命成像和行为方案，将招募具有两个或多个患有主要DSM-5疾病的大型核科。非侵入性连通性神经影像学方法的冒险已经使大脑的内部起作用。大脑的功能和结构连接组在调节从基因到神经元系统再到精神疾病的途径中起关键作用。将基因 - > Connectome HCP方法扩展到基因 - > connectome-> HCP人类疾病中的精神障碍为鉴定可遗传性精神障碍的遗传基础增加了巨大的机会。 ACP提供了一种独特而有力的研究设计，这对于成功的突破至关重要。 ACP将研究来自人群分离株的大型多代家族，这是发现连接组和精神障碍之间遗传联系的有力统计设计。 OOA样品的相对遗传均匀性是独一无二的，其祖先记录在NIH数据库中，可追溯到有限的创建者的14代。该样本在教育背景，生活和工作条件，社会经济地位以及非法药物的影响大大减少的影响下，这一样本也很独特。 OOA社区成员的这些独特特征，结合其较大的家庭规模，使OOA成为有力的人群样本，以研究以家庭遗传模式改变精神疾病中脑连通性的遗传因素。我们将通过精神诊断，广泛的症状和RDOC维度评估行为和认知评估的HCP方案扩展。通过下一代测序和基于家庭的GWAS数据插定，将为所有参与者获得全基因组数据。这些数据将与大型研究社区共享，同时保护参与者的隐私，机密性和福利，并特别注意保护OOA社区的福利。 OOA中的医学遗传发现常规在一般人群样本中被复制，并转化为临床实践。我们受到启发，创造机会，通过共同的数据工作使SUH在脑连接和精神疾病中的成功重复，并组建了一个有效的团队来领导这项工作。