The consortium on the genetics of endophenotypes in schizophrenia: Model recruitment, assessment, and endophenotyping methods for a multisite collaboration
The consortium on the genetics of endophenotypes in schizophrenia: Model recruitment, assessment, and endophenotyping methods for a multisite collaboration
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DOI：
10.1093/schbul/sbl044
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发表时间：
2007-01-01
影响因子：
6.6
通讯作者：
Braff, David L.
中科院分区：
文献类型：
--
作者：
Calkins, Monica E.;Dobie, Dorcas J.;Braff, David L.
背景资料：精神分裂症遗传学联盟（COGS）是一个正在进行的，由美国国家精神卫生研究所资助的7个研究中心合作，调查与精神分裂症相关的定量内表型的发生和遗传结构。本文的目的是提供一个描述的COGS结构和方法，包括参与者招募和评估。研究方法：假设驱动的招募策略包括以下家庭：先证者具有精神障碍诊断和统计手册第四版精神分裂症诊断，并且至少一个未受影响的全同胞可用于基因分型和内表型分型，沿着父母可用于基因分型和内表型分型（可选，取决于年龄）。选择家族结构是为了提供定量内表型特征的对比，从而最大限度地发挥计划遗传分析的作用。先证者是从许多来源招募的，包括临床医生推荐，当地的全国精神病联盟分会，以及通过媒体的广告。所有参与者都接受了标准化的方案，包括临床表征，抽血进行基因分型，以及内表型评估（P50抑制，前脉冲抑制，抗accade性能，连续性能任务，字母-数字跨度，言语记忆和计算机神经认知电池）。研究者参加每周一次的电话会议，以协调和评估招募、临床评估、内表型分析以及数据收集和分析的持续质量控制。数据的完整性是通过使用一个高质量保证，集中的网络数据库。结果如下：截至2006年2月，355个家庭已被招募，688名参与者已被内表型，包括精神分裂症先证者（n = 154，M：F = 110：44），一级生物学亲属（n = 343，M：F = 151：192），和社区比较对象（n = 191，M：F = 81：110）。讨论内容：成功的多中心遗传学合作必须建立标准化的评估和招募方法标准，这些标准定义明确，沟通良好，统一应用。同时，利用内表型的研究需要严格遵守跨研究中心数据采集、设备校准和测试以及软件等效性的标准，并对跨研究中心获得的许多测量结果进行持续质量保证。本报告描述了方法，并提出了作为多位点内表型遗传研究模型的COGS的结构。它还提供了前2年数据收集后的人口统计学信息，其行为数据和内表型表现的遗传学将在未来的文章中充分表征。在下面的评论中讨论的一些问题反映了在精神分裂症内表型的遗传结构研究中评估内表型的挑战。
Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. Methods: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. Results: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). Discussion: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia.