SEARCH FOR DNA MARKERS LINKED TO MANIC DEPRESSIVE ILLNESS IN THE OLD ORDER AMISH

在旧秩序阿米什人中寻找与躁狂抑郁症相关的 DNA 标记

• 批准号: 2578783
• 负责人: E I GINNS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2578783
• 关键词: Mennonite; bipolar depression; child (0-11); chromosomes; computer data analysis; computer simulation; disease /disorder proneness /risk; family genetics; gene expression; genetic markers; genetic models; genotype; human genetic material tag; human subject; human tissue; interview; linkage mapping; longitudinal human study; phenotype

We are performing a genome wide search to identify chromosome regions likely to contain genes that cause bipolar affective disorder (manic depressive illness). One percent of the population is afflicted by this severe cyclical mood disorder, making it one of the most common of the severe mental disorders, and a major public health problem. Moreover, unrecognized or untreated patients with bipolar affective disorder have an approximately 20% risk of death from suicide. We have carried out a systematic genome wide search for genes responsible for bipolar affective disorder in an Old Order Amish kindred of Southeastern Pennsylvania. Although the Old Order Amish generally have the same prevalence of bipolar affective disorder as other populations, for our genetic studies we have utilized several very large extended Amish families where there is an extremely high incidence of bipolar affective disorder over several generations. Large families from a closed population like the Old Order Amish are valuable because they have a reduced number of genes contributing to the illness and we are able to track the illness through the generations. Each gene should also have a larger effect, making them easier to detect. For complex diseases like bipolar affective disorder, each of several genes may increase an individual's susceptibility to develop the disease but any one gene by itself may not be sufficient to cause the full severity of the illness. In studying large numbers of individuals from the general population this presents a very difficult statistical problem since it is likely that different genes cause the illness in different families. Our results suggest that genes on chromosomes 6, 13, and 15, rather than just a single gene, have roles in determining the susceptibility to and severity of bipolar affective disorder. Although the genes causing bipolar affective disorder in the Old Order Amish may also cause illness among non-Amish, it is likely that additional sets of genes are also involved in the susceptibility to develop bipolar affective disorder in other populations.

我们正在进行全基因组搜索， 可能含有导致双相情感障碍（躁狂）的基因 抑郁症）。百分之一的人口受此影响 严重的周期性情绪障碍，使其成为最常见的 严重的精神障碍和重大的公共卫生问题。 此外，委员会认为， 未被识别或未经治疗的双相情感障碍患者， 自杀死亡的风险约为20%。 我们开展一 双相情感障碍基因系统性全基因组搜索 宾夕法尼亚州东南部旧秩序阿米什人亲属的混乱。 虽然旧秩序阿米什人一般有相同的患病率， 双相情感障碍和其他人群一样， 我们利用了几个非常大的阿米什人家庭， 是一个极高的双相情感障碍的发病率超过几个 代像旧秩序那样封闭的大家族 阿米什人很有价值，因为他们的基因数量较少， 我们可以通过追踪疾病的发展 一代又一代 每个基因也应该有一个更大的影响，使他们 更容易被发现。对于像双相情感障碍这样的复杂疾病， 几个基因中的每一个都可能增加个体对 发展疾病，但任何一个基因本身可能不足以 导致疾病的严重性。 在研究大量的 从普通人群中分离出来，这就提出了一个非常困难的问题。 统计问题，因为很可能是不同的基因导致的 不同家庭的疾病 我们的研究结果表明， 染色体6，13和15，而不仅仅是一个单一的基因，有作用， 确定双相情感障碍的易感性和严重程度 disorder.虽然在老年人中引起躁郁症的基因 旧秩序阿米什人也可能导致非阿米什人的疾病，很可能， 另外一些基因组也参与了 在其他人群中发展为双相情感障碍。