Genetics of Bipolar Disorder in Latino Populations

描述(申请人提供)：I型双相情感障碍(BPI)是一种严重的精神疾病，似乎部分由多个易感基因引起，每个易感基因的影响都很小。因此，检测BPI易感基因可能需要对具有多个感染病例的非常大的家系样本进行调查，并将重点放在更多遗传同质性的人群上。我们将在4年内收集385个拉丁裔家庭的诊断信息和DMA样本，每个家庭至少有2个兄弟姐妹感染BPI(DSM-IV诊断)，以检测该人群中的BPI易感基因。我们已经在美国西南部、墨西哥和中美洲组成了一个由7个地点组成的合作伙伴来完成这项任务。每个网站都有专业渠道接触到大量的拉美裔人口，并在拉美裔诊断BPI方面拥有丰富的经验。每个中心将使用机会主义招募机制来确定先证者和家庭，包括精神卫生诊所、医院和患者支持团体等来源。将使用统一的方法对受试者进行诊断，包括对DIGS(遗传学诊断访谈)的盲目访谈，收集相关的医疗记录和实验室测试，以及与每个受试者的近亲进行访谈。将为所有地点提供利用数字挖掘系统进行准确诊断评估的培训，并在研究过程中纳入质量控制方法。将使用最佳估计共识过程来分配最终诊断，每个受试者的临床信息将被输入并存储在中央数据库中。血液样本将从所有被诊断为BPI或其他疾病的家庭成员以及父母双方和(如果无法联系到父母)其他两个兄弟姐妹那里获得。细胞培养和DNA提取将在NIMH指定的遗传研究中心进行。在这笔赠款的第五年，将在CIDR(如果获得批准)进行大约10厘米密度的完整基因组筛查。西南生物医学研究基金会(SFBR)将在BPI受试者中进行基于多点等位基因共享的连锁分析。还将对包含另外750名受试者的一组扩展家系进行二次分析，包括协变量和数量性状分析。与BPI相关的神经认知和结构MRI测试所定义的内表型将在这些家系中得到验证，影响这些生物变量的基因也将通过协变量数量性状分析进行定位。

DESCRIPTION (provided by applicant): Bipolar Disorde, type 1 (BPI) is a severe mental illness that appears to be caused in part by multiple susceptibility genes, each of small effect. Detection of BPI susceptibility genes will thus likely require investigation of a very large sample of pedigrees with multiple affected cases and a focus on more genetically homogeneous populations. We will collect, over 4 years, diagnostic information and DMA samples from 385 families of Latino descent, each with a minimum of 2 siblings affected with BPI (DSM-IV diagnosis) in order to detect BPI susceptibility loci in this population. We have formed a collaboration of 7 sites throughout the Southwest United States, Mexico, and Central America to accomplish this task. Each site has professional access to a large Latino population and extensive experience in diagnosis of BPI in Latinos. Each Center will use an opportunistic recruiting mechanism to ascertain probands and families, including sources such as mental health clinics, hospitals and patient support groups. A uniform approach will be used to diagnose subjects, consisting of blinded interviews with the DIGS (Diagnostic Interview for Genetic Studies), collection of pertinent medical records and laboratory tests, and interview with a close relative of each subject. Training in accurate diagnostic assessment using the DIGS will be provided for all sites and quality control methods will be built into the course of the study. A best estimate consensus process will be used to assign final diagnoses and clinical information for each subject will be entered and stored in a centralized database. Blood samples will be obtained from all family members with a diagnosis of BPI or other, as well as from both parents and (if parents are not available), 2 other siblings. Cell cultures will be created and DMA extracted at the NIMH designated Center for Genetic Studies. In year five of this grant, a complete genome screen at an approximate density of 10 cM will be performed at CIDR (if approved). Linkage analysis based on identification of multipoint allele sharing in BPI subjects will be performed at the Southwest Foundation for Biomedical Research (SFBR). Secondary analyses will also be performed, including covariate and quantitative trait analysis, in a set of extended pedigrees containing an additional 750 subjects. Endophenotypes defined by neurocognitive and structural MRI tests related to BPI will be validated in these pedigrees and genes which contribute to these biologic variables will also be mapped through covariate quantitative trait analyses.