GENETIC LINKAGE STUDIES IN BIPOLAR DISORDERS

双相情感障碍的遗传连锁研究

• 批准号: 6392787
• 负责人: Francis J McMahon
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392787
• 关键词: alcoholism /alcohol abuse; behavioral genetics; bipolar depression; cell line; clinical research; comorbidity; data management; family genetics; gene expression; genetic markers; genetic susceptibility; human genetic material tag; human subject; linkage disequilibriums; linkage mapping; mood disorders; siblings

This application is submitted under the Program Announcement "Collaborative Studies of Mental Disorders." The broad aims are to expand a unique, existing set of pedigrees and test candidate regions for linkage and association with bipolar disorder. For the Johns Hopkins site this represents a revised competing renewal application while for the University of Chicago site this is a new proposal. Together we propose to double the existing family resource by ascertaining an additional 80 moderate-sized families through bipolar I probands with 2 or more siblings affected with recurrent major affective disorders. All participants will be interviewed by trained psychiatrists who have established excellent inter-rater reliability. Diagnoses will be assigned by 2 non-interviewing psychiatrists who review all clinical data. This sample has already proven to be of considerable value to the field. Among clinical findings that have spawned new research directions are our reports of anticipation, parent-of-origin effects, a high prevalence of BPII among the close relatives of the bipolar I probands, and high rates of comorbid panic disorder in a subset of families. This sample provided the first support for previous evidence of linkage to the peri-centromeric region of chromosome 18, the first evidence of linkage to 18q, and the first molecular evidence for a parent-of-origin effect in bipolar disorder. Findings from prospective studies of the 2nd half of this sample demonstrate strikingly high allele-sharing between bipolar II sib pairs at several loci in 18q2l. Exploratory analyses of co- morbid panic disorder and alcoholism have also suggested methods for predicting heterogeneity between bipolar families. In addition to collecting more families, we propose to genotype the existing and additional family sets at candidate regions implicated by a recent genome-wide scan for linkage that has been completed on 68 pedigrees from this sample. We further propose to use standard and innovative linkage and association methods to extract the maximal genetic information needed to locate genes influencing susceptibility to bipolar disorder. This is the most carefully clinically assessed family set in the field. The studies generated from this family resource have already demonstrated its value and have provided testable hypotheses for further work. The enlargement, continued maintenance, and analysis of this unique family resource is important to the field and will form the basis for many future studies.

该申请在计划公告“精神障碍的协作研究”下提交。 广泛的目的是扩展一组独特的，现有的血统和测试候选区域，以连接并与躁郁症相关。 对于约翰·霍普金斯（Johns Hopkins）的网站，这代表了芝加哥大学网站的经修订的竞争续约申请，这是一个新的建议。 我们共同提议通过通过双极I检验来确定另外的80个中等大小的家庭，并具有2个或更多的兄弟姐妹，并患有重复的主要情感障碍。 所有参与者将接受训练有素的精神科医生的采访，这些精神科医生已经建立了良好的评价者可靠性。 诊断将由2名无访视的精神科医生分配，他们审查所有临床数据。 该样本已经证明对该领域具有相当大的价值。 在产生了新的研究方向的临床发现中，我们的预期报告，产物父母的作用，双极I探测器的近亲在近亲中的较高患病率以及在家庭子集中的合并症恐慌症的高率。 该样本为先前的证据提供了与第18q染色体的中心区域联系的先前证据，这是与18Q连接的第一个证据，也是第一个分子证据证明了父母在双相情感障碍中的效应。对该样本第二半的前瞻性研究的发现表明，在18q2l的几个基因座的双极II SIB对之间出现了惊人的等位基因共享。 对病态恐慌症和酒精中毒的探索性分析也提出了预测双极家庭异质性的方法。 除了收集更多的家庭外，我们还建议基于候选区域的现有家庭和其他家庭集，该候选人的现有家族集，该家族涉及最近的全基因组扫描，该连锁已完成该样本的68个谱系。 我们进一步建议使用标准和创新的连锁和关联方法来提取影响对双相情感障碍敏感的基因所需的最大遗传信息。 这是该领域中最仔细评估的家庭。 该家庭资源产生的研究已经证明了其价值，并为进一步工作提供了可检验的假设。 扩大，持续的维护和对这种独特的家庭资源的分析对该领域很重要，并将为许多未来的研究构成基础。