Mapping genes that contribute to bipolar disorder

绘制导致躁郁症的基因图谱

• 批准号: 7136806
• 负责人: Francis J McMahon
• 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/7136806
• 关键词: anxiety disorders; behavioral genetics; biotechnology; bipolar depression; chromosome aberrations; clinical research; family genetics; gene expression; genetic mapping; genetic screening; genetic susceptibility; human subject; interview; linkage mapping; mental health epidemiology; mood disorders; questionnaires; siblings; single nucleotide polymorphism

Bipolar Disorder is a common, often severe mental illness. Family, twin, and adoption studies have demonstrated that genes are the major determinant of individual risk for the disorder, but as in other common disorders, the identification of these genes has proven to be a significant challenge. In collaboration with 10 academic centers across the United States, we have recruited a large sample of families in which at least 2 siblings suffer from bipolar disorder or related mood disorders. This is the largest sample ever to participate in a genetic study of bipolar disorder. All research participants have undergone a diagnostic interview and provided a blood sample for DNA analysis. Genetic linkage studies have been performed using molecular markers evenly spaced across all chromosomes. These studies suggest that regions on chromosomes 8, 6, 13, 17, 18, and 22, among others, may contain genes that contribute to bipolar disorder in these families. Ongoing work is aimed at identifying the actual genes involved. Single nucleotide polymorphisms are being used to identify small chromosomal regions that are overrepresented in people with bipolar disorder. This work has so far identified genes on chromosomes 13, 22, and 18 as the sites of genetic variation that increase risk for bipolar disorder in some people. Related collaborative projects are aimed at investigating genetic variation in candidate genes important in the stress response or regulation of mood or anxiety that may mediate risk for mood and anxiety disorders. In the past year, we have obtained additional evidence supporting association between genes on chromosomes 13 and 22 with risk for bipolar disorder. We have also identified genetic variation in the gene TPH2 that is associated both with bipolar disorder and with suicidal behavior.

双相情感障碍是一种常见且通常严重的精神疾病。家庭、双胞胎和收养研究表明，基因是个体罹患该疾病的风险的主要决定因素，但与其他常见疾病一样，这些基因的识别已被证明是一项重大挑战。我们与美国 10 个学术中心合作，招募了大量家庭样本，其中至少有 2 名兄弟姐妹患有双相情感障碍或相关情绪障碍。这是有史以来参与双相情感障碍基因研究的最大样本。所有研究参与者都接受了诊断访谈，并提供了血液样本进行 DNA 分析。遗传连锁研究是使用所有染色体上均匀分布的分子标记进行的。这些研究表明，第 8、6、13、17、18 和 22 号染色体上的区域可能含有导致这些家族双相情感障碍的基因。正在进行的工作旨在确定所涉及的实际基因。单核苷酸多态性被用来识别双相情感障碍患者中比例过高的染色体小区域。迄今为止，这项工作已确定 13、22 和 18 号染色体上的基因是增加某些人患双相情感障碍风险的遗传变异位点。相关合作项目旨在研究候选基因的遗传变异，这些基因对于压力反应或情绪或焦虑的调节很重要，可能会介导情绪和焦虑症的风险。 去年，我们获得了更多证据，支持 13 号和 22 号染色体上的基因与双相情感障碍风险之间的关联。我们还发现了与躁郁症和自杀行为相关的 TPH2 基因的遗传变异。