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）：阿米什连接组计划 (ACP) 将通过表征大脑回路及其与精神行为和症状维度的关系，将人类连接组计划 (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。从具有跨越诊断界限的多重精神障碍的多代家庭中招募的旧秩序阿米什 (OOA) 成年人的数据将被招募，以使用完整的表型分型。 HCP 寿命成像和行为协议扩展到研究领域标准 (RDoC) 标准 非侵入性连接导向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组在调节中发挥着关键作用。从基因到神经系统再到精神疾病的途径将基因->连接组HCP方法扩展到HCP-人类疾病中的基因->连接组->精神障碍，为识别遗传性精神障碍的遗传基础提供了巨大的机会。 ACP 提供了独特的高效且强大的研究设计，这对于成功突破至关重要。ACP 将研究来自群体分离的大型多代家庭，这是发现连接体特征和精神障碍之间的遗传联系的强大统计设计。该样本的独特之处在于其相对遗传一致性，其祖先记录在 NIH 数据库中，可追溯到十四代有限的创始人。该样本的独特之处还在于其教育背景、生活和工作条件、社会经济地位以及影响力大大降低。经过OOA 社区成员的这些独特特征，加上其庞大的家庭规模，使 OOA 成为研究改变具有家族遗传模式的精神障碍的大脑连接的遗传因素的强大群体样本。通过下一代测序和基于家庭的 GWAS 数据插补，将获得所有参与者的精神病学诊断、广泛症状和 RDoC 维度评估，同时保护参与者。隐私、保密和参与者的福利，特别关注保护 OOA 社区的福利 OOA 的医学遗传发现通常已在一般人群样本中得到复制，并转化为临床实践，我们受到启发，创造机会，让这种成功在大脑中重复。通过共享数据工作，在连接组和精神疾病方面进行研究，并组建了一支高效的团队来领导这项工作。