Genetics of Bipolar Disorder in Latino Populations

拉丁裔人群双相情感障碍的遗传学

基本信息

批准号：
7256904
负责人：
Michael A Escamilla
金额：
$ 128.41万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7256904
关键词：
Affect All Sites Alleles Amygdaloid structure Anterior Biological Biomedical Research Bipolar Disorder Blinded Blood specimen Cells Central America Clinical Clinical Data Clinics and Hospitals Collaborations Collection Communities Consensus Contracts Cultured Cells DNA DSM-IV Data Databases Detection Diagnosis Diagnostic Disease Family Family member Foundations Future Genes Genetic Genome Genotype Grant Heterogeneity Hispanics Individual Information Dissemination Interview Investigation Laboratories Latino Left Magnetic Resonance Imaging Manuals Maps Measures Medical Medical Records Memory Mental Health Mental disorders Methods Mexican Mexico Monitor National Institute of Mental Health Neurocognitive Parents Patients Performance Phenotype Population Predisposition Process Protocols documentation Psychiatrist Quality Control Quantitative Trait Loci Rate Records Recruitment Activity Relative (related person)Research Personnel Sampling Shipping Ships Siblings Site Source Southwestern United States Structure Support Groups Susceptibility Gene Symptoms Testing Training United States Validation Verbal Learning base clinical Diagnosis computerized density design endophenotype executive function experience family structure genetic analysis genetic linkage analysis genetic pedigree lymphoblastoid cell line proband repository severe mental illness statistics trait

项目摘要

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.

描述（由申请人提供）：双极疾病，类型1（BPI）是一种严重的精神疾病，似乎部分由多个易感基因（每个易感性基因）引起。因此，检测BPI敏感性基因可能需要研究具有多个受影响病例的大量血统样本，并关注更遗传均匀的人群。我们将在4年中收集来自385个拉丁裔血统家族的诊断信息和DMA样本，每个家庭至少有2个受BPI（DSM-IV诊断）影响的兄弟姐妹，以检测该人群中的BPI敏感性基因座。我们在整个美国西南部，墨西哥和中美洲建立了7个站点，以完成这项任务。每个站点都可以专业地访问大量拉丁裔人口，并且在拉丁美洲人的BPI诊断方面具有丰富的经验。每个中心将使用机会主义的招聘机制来确定概率和家庭，包括精神卫生诊所，医院和患者支持小组等来源。一种统一的方法将用于诊断受试者，包括对DIGS的盲目访谈（遗传研究的诊断访谈），相关医疗记录和实验室测试的收集以及每个受试者的近亲进行访谈。将在所有站点进行精确诊断评估培训，并将在研究过程中内置质量控制方法。最佳的估计共识过程将用于分配最终诊断，每个受试者的临床信息将被输入并存储在集中式数据库中。将从所有有BPI或其他诊断的家庭成员以及父母双方（如果父母不可用的话）和其他2个兄弟姐妹那里获得血液样本。将创建细胞培养物，并在NIMH指定的遗传研究中心提取DMA。在这笔赠款的第五年中，将在CIDR（如果获得批准）进行大约10 cm密度的完整基因组筛选。基于BPI受试者中多点等位基因共享的识别的链接分析将在西南生物医学研究基金会（SFBR）进行。还将在一组额外的750名受试者中进行二级分析，包括协变量和定量性状分析。由与BPI相关的神经认知和结构MRI测试定义的内表型将在这些谱系和基因中得到验证，这些基因和基因也将通过协方差定量性状分析来映射这些生物学变量。