Global studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-Consortium

摘要 白色物质（WM）回路是人脑中神经元通信的基础， 所有主要精神、神经和发育状况的异常。ENIGMA联盟 已经进行了最大的，最有力的协调研究WM微观结构的变化， 以及几种主要的精神疾病我们已经发现了 迄今为止，我们对严重精神疾病进行的最有力、最具国际代表性的研究存在缺陷， 包括精神分裂症（SCZ）、双相情感障碍（BD）和重度抑郁症（MDD）。中的重叠 这些疾病的微结构变异模式也与遗传风险的重叠相关， 大规模的GWAS。ENIGMA联盟中的这些新发现激发了一个强大的， 严格的，深入的研究疾病和遗传效应的WM束和电路牵连在严重的精神疾病， 疾病。在这里，我们发起了一项倡议，联合神经成像协调领域的领导者， 分析，扩散连接，精神病学，精神遗传学，统计遗传学，神经影像遗传学， 工作流自动化，人工智能和分布式数据科学。我们提出的工作将扩大合作研究 绘制大脑成像生物标志物和驱动潜在的精神疾病风险脆弱性的可变性， 病我们所有的研究结果都将公开，就像之前所有的ENIGMA研究一样。这里我们扩展方法 通过NeuroDISK -一个本体集成的用户- 友好的平台，用于基于队列水平元数据的用户驱动的子分析。这一创新框架 支持持续的数据整合和更新调查结果。在我们的具体目标中，我们的多学科和 高效的研究团队将：1）执行全球协调的微观结构度量GWAS， 在发现和复制框架中，对所有年龄段的10万多人进行了扩散MRI扫描; 2） 分发一种新的人工智能驱动的协议，以提取和质量控制中矢状胼胝体指标， 更常用的T1加权结构MRI，用于绘制和协调发育轨迹 胼胝体的成熟和退化在整个生命周期;我们将容纳MRI数据的研究和 临床质量，并确定胼胝体厚度，面积和曲率的遗传结构; 3）构建一个 集成的ENIGMA-DSI Studio管道提供高通量纤维束成像和光纤分析方法， DSI-Studio软件用于识别SCZ、BD、MDD上ENIGMA工作组的结构性连接障碍; 4） 分发和传播公开可用的集装箱化纤维束成像和纤维分析协议， 获取具体的考虑因素，并在我们的新的连续数据集成和分析的手段， NeuroDISK框架。

ABSTRACT White matter (WM) circuitry is the basis for neuronal communication in the human brain and exhibits robust abnormalities in all major psychiatric, neurological, and developmental conditions. The ENIGMA consortium has already performed the largest, most well-powered coordinated studies of WM microstructural variability within and across several major mental disorders and illnesses. We have already discovered common patterns of deficits in our most highly powered, and internationally representative studies of severe mental illnesses to date, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). The overlap in the patterns of microstructural variation in these disorders also correlate with the overlap in genetic risk suggested by large scale GWAS. These emerging findings within the ENIGMA consortium motivate a highly-powered, rigorous, and in-depth study of disease and genetic effects on WM tracts and circuits implicated in severe mental illnesses. Here we launch an initiative that unites leaders in the fields of neuroimaging harmonization and analysis, diffusion connectivity, psychiatry, psychiatric genetics, statistical genetics, neuroimaging genetics, workflow automation, and AI and distributed data science. Our proposed work will extend the collaborative study of mapping brain-imaging biomarkers and the variability that drives underlying vulnerability to risk of mental illness. All our findings will be made publicly available, as in all prior ENIGMA studies. Here we extend methods for the public distribution and dissemination of findings through NeuroDISK - an ontologically integrated, user- friendly platform, for user-driven sub-analyses based on cohort level meta-data. This innovative framework enables continuous data integration and updating of findings. In our Specific Aims, our multidisciplinary and highly productive team of investigators will: 1) perform a global coordinated GWAS of microstructure metrics in over 100,000 individuals of all ages scanned with diffusion MRI in a discovery and replication framework; 2) distribute a novel AI-driven protocol to extract and quality control the midsagittal corpus callosum metrics from the more commonly collected, T1-weighted structural MRIs, to map and harmonize developmental trajectories of callosal maturation and degeneration across the lifespan; we will accommodate MRI data of research and clinical quality, and identifying genetic architecture for callosal thickness, area, and curvature; 3) constructing an integrated ENIGMA-DSI Studio pipeline offering high-throughput tractography and fiber analytic methods on the DSI-Studio software to identify structural dysconnectivity in ENIGMA working groups on SCZ, BD, MDD; 4) distribute and disseminate publicly available, containerized tractography and fiber analytic protocols with image acquisition specific considerations, and means for continuous data integration and analyses in our novel NeuroDISK framework.