The bipolar disorder phenome database: A resource for genetic studies
The bipolar disorder phenome database: A resource for genetic studies
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DOI：
10.1176/appi.ajp.2007.06122045
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发表时间：
2007-08-01
影响因子：
17.7
通讯作者：
McMahon, Francis J.
中科院分区：
文献类型：
--
作者：
Potash, James B.;Toolan, Jennifer;McMahon, Francis J.
目标：本研究的目的是收集和验证从双相情感障碍家庭收集的表型变量数据库，作为遗传和其他生物学研究的资源。方法：确定两项双相情感障碍遗传连锁研究的参与者：芝加哥大学、约翰·霍普金斯大学和美国国立心理健康研究所（NIMH）校内项目（CHIP）合作和NIMH遗传学倡议项目。所有参与者都接受了详细的表型评估，使用情感障碍和精神分裂症-终身版本的时间表或遗传研究诊断访谈的四个版本之一。临床医生审查了访谈项目和用于从原始数据集中提取数据的衍生变量定义。对合并数据进行范围和逻辑评估，并根据原始数据重新验证子集。不一致的数据和被认为不可靠的变量被排除。几个由此产生的变量的特点是在总队列和测试的家族聚集性，遗传力，和统计权力的遗传连锁和关联studies.Results：合并数据库的表型变量包含197个变量的5,721名受试者在1,177个家庭。其中5 373名受试者的脱氧核糖核酸（DNA）样本可用。双相情感障碍的临床表现差异很大。大多数受试者患有严重的疾病，往往致残。许多表型变量具有很强的家族性，一些数量变量具有很强的遗传性。在这项研究中组装的队列提供了大量的权力进行遗传连锁和关联研究，使用特定的临床特征作为协变量或作为主要phenotypes.Conclusions：这是最大的表型变量数据库尚未组装双相情感障碍，它现在是提供给研究界。研究人员和临床医生可以使用这个数据库来探索一个队列中的现象学和遗传学之间的联系，这个队列有足够的能力来检测双相情感障碍中即使是适度的遗传效应。
objective: The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies.Method: Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies. Clinicians reviewed the interview items and derived variable definitions that were used to extract data from the original datasets. The combined data were subjected to range and logic assessments, and a subset was re-verified against the original data. Inconsistent data and variables that were deemed unreliable were excluded. Several of the resulting variables were characterized in the total cohort and tested for familial clustering, heritability, and statistical power in genetic linkage and association studies.Results: The combined database of phenotypic variables contained 197 variables on 5,721 subjects in 1,177families. Deoxyribonucleic acid (DNA) samples are available for 5,373 of these subjects. The clinical presentation of bipolar disorder varied markedly. Most subjects suffered from serious and often disabling illness. Many phenotypic variables are strongly familial, and some quantitative variables are highly heritable. The cohort assembled in this study offers substantial power to carry out genetic linkage and association studies that use specific clinical features as covariates or as primary phenotypes.Conclusions: This is the largest database of phenotypic variables yet assembled for bipolar disorder, and it is now available to the research community. Researchers and clinicians can use this database to explore the connections between phenomenology and genetics in a cohort that is adequately powered to detect even modest genetic effects in bipolar disorder.