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 确定包含双相情感相关基因的染色体区域 情感障碍(BPAD，躁郁症)。大致 1%的人口受到这种严重周期性疾病的困扰。 情绪障碍和未经治疗的BPAD患者 自杀死亡风险约为20%。我们正在学习 几个来自旧秩序阿米什人的大家庭 BPAD的发病率在几代人中甚至更高。 在这些旧秩序的阿米什家庭中，可能有更有限的 导致情感障碍的不同基因的数量 表型。除了已报道的与BPAD的其他联系外， (即染色体4p、4q、11、12、18q、21、22和X)，我们的结果 提示染色体6p SIBPAL(p&lt；0.0001)上的基因， 13号染色体SIBPAL(p=0.0003)，15号染色体 SIBPAL(p=0.0003)，在增加易感性方面起作用 双相情感障碍。此外，与其限制我们的 全基因组搜索以确定BPAD的易感基因 检验了“保护性”等位基因可能对 无精神疾病(即精神健康“健康”) 这些“高危”家庭中未受影响的家庭成员。我们发现 染色体4p SIBPAL(p&lt；0.00001； 和4Q SIBPAL(p&lt；0.001； GENEHUNTER NPL=4.7)与心理健康有关 健康状况表明某些等位基因可以防止或改变 BPAD的临床表现。身份识别和 易感基因和“保护性”等位基因的特征应导致 发展更合理和更直接的方法来 情感障碍的有效治疗。

We are carrying out a genome-wide search to identify chromosome regions that contain genes involved in bipolar affective disorder (BPAD, manic depressive illness). Approximately one percent of the population is afflicted by this severe cyclical mood disorder and untreated patients with BPAD have an approximately 20% risk of death from suicide. We are studying several large families from the Old Order Amish population where there is an even higher incidence of BPAD over several generations. In these Old Order Amish families there may be a more limited number of different genes contributing to the affective disorder phenotype. In addition to the other reported linkages for BPAD, (i.e. to chromosomes 4p, 4q, 11,12,18q, 21,22 and X), our results suggest that genes on chromosome 6p SIBPAL (p<0.0001), chromosome 13 SIBPAL (p=0.0003), and chromosome 15 SIBPAL (p=0.0003), have roles in increasing the susceptibility to bipolar affective disorder. Also, rather than limiting our genome-wide search to identifying susceptibility loci for BPAD, we tested the hypothesis that "protective" alleles may contribute to the absence of psychiatric illness (i.e., mental health "wellness") in unaffected family members in these "high risk" families. We found strong evidence for loci on chromosome 4p SIBPAL (p<0.00001; GENEHUNTER NPL=3.8) and 4q SIBPAL (p<0.001; GENEHUNTER NPL=4.7) that are linked to mental health wellness suggesting that certain alleles could prevent or modify the clinical manifestations of BPAD. The identification and characterization of susceptibility and "protective" alleles should lead to the development of more rational and direct approaches to effective therapy for affective disorders.