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

我们正在进行全基因组搜索以确定染色体区域 可能含有导致双相情感障碍(躁狂症)的基因 抑郁症)。1%的人口受到这种疾病的困扰 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，也是一个重大的公共卫生问题。此外， 未被识别或未治疗的双相情感障碍患者 大约20%的自杀死亡风险。我们已经开展了一项 系统的全基因组搜索双相情感相关基因 宾夕法尼亚州东南部的一个旧秩序中的阿米什家族的混乱。 尽管旧教派的阿米什人普遍有同样的 双相情感障碍与其他人群一样，用于我们的遗传学研究 我们利用了几个非常大的阿米什家族， 是一种双相情感障碍的极高发病率 几代人。像旧秩序这样来自封闭人口的大家庭 阿米什人很有价值，因为他们的基因数量减少了 导致了这种疾病，我们能够通过 世世代代。每个基因也应该有更大的影响，使它们 更容易察觉。对于像双相情感障碍这样的复杂疾病， 几种基因中的每一种都可能增加个体对 但任何一个基因本身都可能不足以导致 导致疾病的全部严重程度。在研究大量的 从一般人群中的个人来看，这是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了 不同家庭的疾病。我们的结果表明，基因在 6号、13号和15号染色体，而不仅仅是单个基因，在 确定双相情感障碍的易感性和严重程度 无序。尽管导致双相情感障碍的基因 旧秩序阿米什人也可能在非阿米什人中引起疾病，很可能是 另外一组基因也与易感性有关。 在其他人群中发展为双相情感障碍。

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.