Genetics of Bipolar Disorder in Latino Populations

描述（由申请人提供）：双相情感障碍1型（BPI）是一种严重的精神疾病，似乎部分由多种易感基因引起，每种易感基因的影响都很小。因此，BPI易感基因的检测可能需要对具有多个受影响病例的非常大的家系样本进行调查，并关注遗传上更同质的人群。我们将在4年内收集来自385个拉丁裔家庭的诊断信息和DMA样本，每个家庭至少有2个兄弟姐妹患有BPI（DSM-IV诊断），以检测该人群中的BPI易感基因座。我们在美国西南部、墨西哥和中美洲的7个地点建立了合作关系，以完成这项任务。每个网站都有专业的访问大量的拉丁美洲人口和丰富的经验，诊断BPI在拉丁美洲人。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。将使用统一的方法诊断受试者，包括与DIGS（遗传学研究诊断访谈）进行盲态访谈、收集相关病历和实验室检查以及与每例受试者的近亲进行访谈。将为所有研究中心提供使用DIGS进行准确诊断评估的培训，并将质量控制方法纳入研究过程。将使用最佳估计共识流程分配最终诊断，并将每例受试者的临床信息输入并存储在集中数据库中。将从诊断为BPI或其他的所有家庭成员以及父母和（如果父母不可用）其他2名兄弟姐妹中采集血样。将在NIMH指定的遗传研究中心创建细胞培养物并提取DMA。在该补助金的第五年，将在CIDR（如果获得批准）进行大约10 cM密度的完整基因组筛查。将在西南生物医学研究基金会（SFBR）进行基于BPI受试者中多点等位基因共享鉴定的连锁分析。还将在一组包含额外750例受试者的扩展家系中进行次要分析，包括协变量和数量性状分析。通过与BPI相关的神经认知和结构MRI测试定义的内表型将在这些家系中进行验证，并且有助于这些生物变量的基因也将通过协变量定量性状分析进行映射。

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.