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（由申请人提供）：阿米什连接组项目（ACP）将通过表征大脑回路及其与精神病行为和症状维度的关系，将人类连接组项目（HCP）扩展到精神疾病。我们建议收集HCP连接组学和全基因组测序数据，在旧秩序阿米什人（OOA）的成年人招募多代家庭与多重精神障碍跨越诊断界限。将招募具有两个或更多个严重DSM-5疾病成员的大型核心家族，使用扩展到研究领域标准（RDoC）标准的完整HCP寿命成像和行为方案进行表型分析。非侵入性的面向连接的神经成像方法的出现为大脑的内部运作提供了新的线索。大脑的功能和结构连接体在调节从基因到神经系统再到精神疾病的通路中起着关键作用。将基因-->连接体HCP方法扩展到HCP-人类疾病中的基因-->连接体-->精神障碍，为识别遗传性精神障碍的遗传基础增加了巨大的机会。ACP提供了一个独特的高效和强大的研究设计，这是成功突破的关键。ACP将研究来自人群隔离的大型多代家庭，这是一个强大的统计设计，用于发现连接特征和精神障碍之间的遗传联系。OOA样本在其相对遗传一致性方面是独一无二的，其祖先记录在NIH数据库中，可追溯到14代有限的创始人。这一样本的独特之处还在于其教育背景、生活和工作条件、社会经济地位相对一致，而且受非法药物的影响也小得多。OOA社区成员的这些独特特征，加上他们庞大的家庭规模，使得OOA成为研究改变具有家族遗传模式的精神障碍患者大脑连接的遗传因素的有力人群样本。我们将在HCP方案的基础上扩展精神病诊断、广泛症状和行为和认知的RDoC维度评估。将通过下一代测序和基于家族的GWAS数据插补获得所有参与者的全基因组数据。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，特别注意保护OOA社区的福利。OOA中的医学遗传学发现已在一般人群样本中进行常规复制，并转化为临床实践。我们受到启发，通过共享数据的努力，创造机会，让大脑连接体和精神疾病的成功重复，并组建了一个高效的团队来领导这一奋进。