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

我们一直在进行全基因组搜索以确定染色体 包含双相情感障碍易感基因的区域 (躁郁症)。大约百分之一的人口 受到这种严重的周期性情绪障碍的困扰，使其成为 最常见的严重精神障碍，和主要的公共卫生 有问题。此外，未被识别或未治疗的双相情感障碍患者 情感性精神障碍有大约20%的自杀死亡风险。 我们已经对易感性进行了系统的全基因组搜索 一个古老的阿米什大家族中双相情感障碍的基因 位于宾夕法尼亚州东南部。尽管旧秩序的阿米什人一般 双相情感障碍的患病率与其他人相同 在我们的遗传研究中，我们利用了几个非常大的 有极高发病率的阿米什大家庭 几代人的双相情感障碍。来自中国的大家庭 像旧秩序阿米什这样封闭的人口是有价值的，因为他们 导致这种疾病的基因数量应该比较有限 我们能够通过世代追踪这种疾病。每个基因 也应该有更大的影响，使它们更容易被发现。为 像双相情感障碍这样的复杂疾病，每一个都有几个基因 可能会增加个人患上这种疾病的易感性，但 任何一个基因本身都可能不足以导致全部严重程度 关于这种疾病的。在研究大量来自 一般人口这是一个非常困难的统计问题 因为很可能是不同的基因导致了不同的疾病 家人。我们的初步结果表明，6号染色体上的基因 (P&lt；0.0001)，13号染色体(p=0.0003)，15号染色体(p=0.0003)， 而不只是单个基因，它们在决定 易患双相情感障碍。我们还在进行基因分型 其他组拥有的感兴趣区域的其他标记 据报道含有双相情感障碍的易感基因， 包括4P、12、18Q、21、22和X染色体上的那些。 导致旧秩序阿米什人双相情感障碍的基因也可能 在非阿米什人中引起疾病，很可能是额外的一组 基因也与双相情感障碍的易感性有关。 其他人群中的情感障碍。我们一直在进行基因组测试 广泛搜索以确定包含易感性的染色体区域 双相情感障碍(躁郁症)的基因。 大约百分之一的人口受到这种严重疾病的困扰。 周期性情绪障碍，使其成为最常见的严重 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 系统性全基因组搜索双相情感障碍易感基因 东南部一个古老的阿米什大家族的情感障碍 宾夕法尼亚州。尽管旧秩序的阿米什人一般都有同样的 与其他人群一样，双相情感障碍的患病率 基因研究，我们利用了几个非常大的扩展的阿米什人 双相情感障碍发生率极高的家庭 几代人的精神错乱。来自封闭的大家庭 像旧秩序亚米希人这样的人口是有价值的，因为他们应该 导致这种疾病的基因数量更有限，我们 能够代代相传地追踪这种疾病。每个基因都应该 也有更大的影响，使它们更容易被发现。对于复杂的 像双相情感障碍这样的疾病，几个基因中的每一个都可能 增加个人患上这种疾病的易感性，但任何 一个基因本身可能不足以导致完全严重的 他的病。从总体上研究大量的个体 这是一个非常困难的统计问题，因为它 可能是不同的基因在不同的家庭中导致了这种疾病。 我们的初步结果表明，6号染色体上的基因(p&lt；0.0001)， 13号染色体(p=0.0003)和15号染色体(p=0.0003)，而不仅仅是 单个基因在决定双相情感障碍的易感性方面起作用 情感障碍。我们还在对更多的标记进行基因分型 其他组织报告包含的有趣区域 双相情感障碍的易感基因，包括 染色体4p、12、18q、21、22和X。 旧教派中的双相情感障碍也可能导致疾病 在非阿米什人中，很可能额外的一组基因也是 与患双相情感障碍的易感性有关 其他种群。

We have been performing a genome wide search to identify chromosome regions that contain susceptibility genes for bipolar affective disorder (manic depressive illness). Approximately 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 susceptibility genes for bipolar affective disorder in a large 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 should have a more limited 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 initial results suggest that genes on chromosome 6 (p<0.0001), chromosome 13 (p=0.0003), and chromosome 15 (p=0.0003), rather than just a single gene, have roles in determining the susceptibility to bipolar affective disorder. We are also genotyping additional markers on interesting regions that other groups have reported to contain susceptibility genes for bipolar affective disorder, including those on chromosomes 4p, 12, 18q, 21, 22 and X. 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.We have been performing a genome wide search to identify chromosome regions that contain susceptibility genes for bipolar affective disorder (manic depressive illness). Approximately 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 susceptibility genes for bipolar affective disorder in a large 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 should have a more limited 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 initial results suggest that genes on chromosome 6 (p<0.0001), chromosome 13 (p=0.0003), and chromosome 15 (p=0.0003), rather than just a single gene, have roles in determining the susceptibility to bipolar affective disorder. We are also genotyping additional markers on interesting regions that other groups have reported to contain susceptibility genes for bipolar affective disorder, including those on chromosomes 4p, 12, 18q, 21, 22 and X. 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.