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: 6111168
• 负责人: EDWARD 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/6111168
• 关键词: Mennonite; bipolar depression; child (0-11); chromosomes; clinical research; disease /disorder proneness /risk; family genetics; genetic markers; genotype; human genetic material tag; human subject; human tissue; interview; linkage mapping; longitudinal human study; mental health epidemiology; phenotype

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.

我们正在进行全基因组搜索， 识别包含双极相关基因的染色体区域 情感障碍（BPAD，躁狂抑郁症）。约 百分之一的人口受到这种严重的周期性疾病的折磨， 情绪障碍和未经治疗的BPAD患者 自杀死亡的风险约为20%。我们正在研究 几个来自旧秩序阿米什人的大家庭， 在几代人中，BPAD的发病率甚至更高。 在这些旧秩序阿米什家庭可能有一个更有限的 导致情感障碍的不同基因的数量 表型除了所报告的与《巴塞尔公约》和《巴塞尔公约》评估和评价局的其他联系外， (i.e.染色体4p，4 q，11，12，18 q，21，22和X），我们的结果 提示染色体6p上的基因SIBPAL（p<0.0001）， 13号染色体SIBPAL（p=0.0003）和15号染色体 SIBPAL（p=0.0003）在增加对以下疾病的易感性方面发挥作用： 双相情感障碍此外，与其限制我们 全基因组搜索以确定BPAD的易感基因座，我们 测试了“保护性”等位基因可能有助于 没有精神疾病（即，心理健康（wellness） 这些“高风险”家庭中未受影响的家庭成员。我们发现 强有力的证据表明染色体4p上的基因座SIBPAL（p<0.00001; GENEHUNTER NPL=3.8）和4q SIBPAL（p<0.001; GENEHUNTER NPL=4.7）与心理健康有关 健康表明某些等位基因可以阻止或改变 BPAD的临床表现。确定和 易感性和“保护性”等位基因的特征应导致 制定更合理和直接的方法， 情感障碍的有效疗法