A COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDER

双相情感障碍的合作基因组研究

• 批准号: 6392431
• 负责人: William Henry Coryell
• 金额: $ 25.71万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392431
• 关键词: behavioral genetics; bipolar depression; cell line; clinical research; computer assisted sequence analysis; computer data analysis; computer program /software; cryopreservation; diagnosis quality /standard; family genetics; genetic markers; genetic registry /resource /referral center; genetic susceptibility; genome; genotype; human data; human genetic material tag; human subject; information systems; interview; linkage mapping; mental disorder diagnosis; phenotype

DESCRIPTION: (Adapted from investigator's abstract) Bipolar affective disorder is a severe heritable condition affecting about one percent of the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. Genetic linkage studies have not been robust although some reports of linkages have been replicated several times. The NIMH began a national archival database for search of linked genes in this condition in 1988. Its purpose was to collect a large sample of interviews and cell lines from families suitable for linkage and association studied. Four centers participated in the initiative: Indiana University, John Hopkins University, Washington University of St. Louis, and the NIMH Intramural Program. A new structured polydiagnostic interview, the Diagnostic Interview for Genetic Studies (DIGS), was developed and field-tested. Ascertainment was begun in 1999 to identify Bipolar I (BPI) probands with a BPI or Schizoaffective, Bipolar type (Sa/BP) first degree relative. Two hundred and forty-three families have been enrolled in the program including 1025 affected subjects. Twenty on hundred sixty five structured interviews have been given and 2097 immortalized cell lines have been cryopreserved. A genomic survey has been completed on 540 subjects selected from 97 families and eight candidate areas for linkage have been identified, some supporting previous findings. These cell lines and related clinical information has been publicly released. A follow-up sample is presently being genotyped, with particular attention to areas of interest identified in the original survey. It is proposed to extend the present study through families identified by a BPI/BPI sib pair at eight sites (Indiana, Washington University of St. Louis, Johns Hopkins, University of Pennsylvania, University of California, San Diego , University of Utah, University of Chicago, and University of Iowa). A total of 450 new families and 2500 cell lines and interviews over the next four years will be added. This sample will be used to confirm and extend present findings of linkage, to narrow the implicated regions, and to test candidate genes. Genotypes will be shared with a consortium of investigators studying linkage in bipolar illness. Cell lines and interview data will be made freely available to the scientific community.

描述：（改编自研究者的摘要）双相情感 疾病是一种严重的遗传性疾病，影响约百分之一的人 人口。人们对遗传模式知之甚少，并且可能 涉及多个小到中度影响的位点。遗传连锁 尽管有一些关于联系的报告，但研究并不充分 重复了几次。 NIMH 建立了国家档案数据库 1988年在这种情况下搜索连锁基因。其目的是 从合适的家庭收集大量访谈样本和细胞系 用于研究链接和关联。四大中心参与 倡议：印第安纳大学、华盛顿约翰霍普金斯大学 圣路易斯大学和 NIMH 校内项目。一个新的结构 多诊断访谈，基因研究的诊断访谈 （DIGS），已开发并经过现场测试。 1999 年开始确定 识别具有 BPI 或分裂情感、双相情感障碍的双相 I (BPI) 先证者 类型 (Sa/BP) 一级亲属。两百四十三个家庭 已登记参加该计划，包括 1025 名受影响的受试者。二十 已进行 165 次结构化访谈，2097 永生化细胞系已被冷冻保存。一项基因组调查已经 完成从 97 个家庭和 8 名考生中选出的 540 个科目 已经确定了联系领域，其中一些领域支持了先前的发现。 这些细胞系及相关临床信息已公开 释放。 目前正在对后续样本进行基因分型，其中 特别注意原件中确定的感兴趣领域 民意调查。 建议将本研究扩展到由以下人员确定的家庭 八个地点的 BPI/BPI 同胞对（印第安纳州、华盛顿大学、圣路易斯大学） 圣路易斯，约翰霍普金斯大学，宾夕法尼亚大学，大学 加利福尼亚大学、圣地亚哥大学、犹他大学、芝加哥大学和 爱荷华大学）。总共450个新家族和2500个细胞系 未来四年将增加采访。该样本将是 用于确认和扩展目前的联系发现，以缩小范围 相关区域，并测试候选基因。基因型将被共享 与研究躁郁症之间联系的研究人员联盟合作。 细胞系和访谈数据将免费提供给 科学界。