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，以确定包含双相情感障碍（BPAD，躁狂抑郁症）相关基因的染色体区域。大约1%的人患有这种严重的复发性情绪障碍，未经治疗的BPAD患者有大约20%的自杀死亡风险。我们正在研究几个来自旧秩序阿米什人的大家庭，他们几代人的BPAD发病率非常高。在这些旧秩序阿米什家族中，可能有更有限数量的不同基因导致情感障碍表型。除了已报道的其他与BPAD相关的基因（即4p、4q、11,12,18q、21,22和X染色体）外，我们的研究结果表明，6p染色体上的基因SIBPAL （p<0.0001）、13染色体上的基因SIBPAL （p=0.0003）和15染色体上的基因SIBPAL （p=0.0003）在增加双相情感障碍的易感性中起作用。此外，我们并没有将我们的全基因组搜索限制在确定BPAD的易感性位点上，而是测试了保护性等位基因可能有助于这些高风险家庭中未受影响的家庭成员没有精神疾病（即心理健康）的假设。我们发现强有力的证据表明，4p染色体上的SIBPAL位点（p<0.00001; GENEHUNTER NPL=3.8）和4q染色体上的SIBPAL位点（p<0.001; GENEHUNTER NPL=4.7）与心理健康有关，这表明某些等位基因可以预防或改变BPAD的临床表现。易感性和保护性等位基因的鉴定和表征将导致开发更合理和直接的方法来有效治疗情感障碍。-双相情感障碍，躁狂抑郁症，自杀，联系，心理健康，易感性，保护性等位基因

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 recurrent 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 a very high 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. - bipolar affective disorder, manic depressive illness, suicide, linkages, mental health wellness, susceptibility, protective alleles