GENETICS OF BIPOLAR DISORDER IN LATINO POPULATIONS

拉丁裔人群双向情感障碍的遗传学

基本信息

批准号：
7627546
负责人：
Michael A Escamilla
金额：
$ 1.21万
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：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7627546
关键词：
Affect Amygdaloid structure Anterior Atlases Bipolar Disorder Brain Brain region Cerebral aqueduct Cerebrospinal Fluid Computer Retrieval of Information on Scientific Projects Database DNA DSM-IV Data Diagnosis Diagnostic Family Family member Funding Generations Genes Genetic Goals Grant Gray unit of radiation dose Hispanics Image Individual Institution Laboratories Latino Left Magnetic Resonance Magnetic Resonance Imaging Maps Measurement Measures Methods Neurocognitive Patients Population Positioning Attribute Predisposition Procedures Protons Publishing Range Relative (related person)Reporting Research Research Personnel Resources Sample Size Sampling Scanning Series Siblings Site Slice Source Standards of Weights and Measures Structure Testing Thick Three-Dimensional Image Three-Dimensional Imaging Time Training United States National Institutes of Health Weight base case control density endophenotype experience genetic pedigree gray matter interest size trait white matter

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The goal of this project is to collect diagnostic information and DNA samples from 385 families of Latino descent, each with a minimum of two siblings affected with BPI (DSM-IV diagnosis) in order to detect BPI susceptibility loci in this population. 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. RESEARCH PLAN AND METHODS: Imaging data will be acquired for a subset of subjects (from approximately 30 families) at the San Antonio site in order to validate structural imaging measures as endophenotypes. We will obtain MRIs for approximately 60 subjects a year (15 siblings with BPI, 30 unaffected siblings, and 15 controls) over a four year period. We have extensive experience in obtaining these MRIs for BP subjects and controls and have done so for 140 subjects over the last two years. We will use a GE/Elscint Prestige 2-T high-field magnetic resonance (MR) scanner, located at the UTHSCSA Research Imaging Center (RIC). The scans will be performed by a highly trained MR technician. A sagittal scout series is first obtained to verify patient position, image quality, and clarity of the full extent of the aqueduct of sylvius to locate a midline sagittal image. 3D T1-FFE (T-1 weighted fast field echo) will be performed in the coronal plane with TR of 25 ms, TE of 5 ms, flip angle of 40o, field of view (FOV) 240 mm x 220 mm, slice thickness of 1.0 mm, NEX=2 and matrix size of 256x192, to obtain images covering the entire brain. We will additionally use a spin echo sequence to obtain T2 and proton density images in the axial plane and screen for neuroradiological abnormalities. The total time to collect the 3D T1-FFE and spin echo sequence is approximately 25 minutes. The proposed regions-of-interest (ROIs) will be identified and delineated according to previously published methods for anatomical MRI measurements of these particular brain regions. The anatomical regions will be identified in 3 anatomical planes, in reference to standard anatomical brain atlases, and examination of the three-dimensional volume-rendered view of these structures will be used to facilitate identification of boundaries. All morphometric measures will be performed in the laboratory of Dr. Jair Soares by raters well trained to do these specific procedures, and who have achieved inter-rater reliability of over 0.90 for these specific measurements. The volume of gray and white matter and cerebrospinal fluid (CSF) in the brain ROIs will be estimated using the 3D T1-FFE MRI data and a semi-automated segmentation method based on the generation of histogram of gray, white matter and cerebrospinal fluid pixel intensities. This method uses a histogram approach to determine the thresholds for separation of gray matter, white matter, and CSF, as per method previously described 180,181186,187. With the proposed sample size of 60 affected individuals and 60 healthy comparison subjects, we will have 80% power (1-b%) to reject the null hypothesis (a=0.05) of no between group difference for a contrast with small effect size (minimum effect size = 0.25). Given the effect sizes of case-control contrast for the anterior cingulate (effect size=1.08) and left amygdala (effect size=0.64) reported above, we anticipate power to detect between group differences to vary from 96 to 99.9%. Assuming that volumetric measurements for unaffected relatives are midway between affected and unrelated individuals, with 120 unaffected family members and 60 healthy comparison subjects, we anticipate power to detect between group differences to range from 59 to 99.6%, depending on the ROI.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目和研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。目的：该项目的目标是从 385 个拉丁裔家庭收集诊断信息和 DNA 样本，每个家庭至少有两个兄弟姐妹患有 BPI（DSM-IV 诊断），以便检测该人群中的 BPI 易感位点。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中得到验证，而有助于这些生物变量的基因也将通过协变量数量性状分析进行映射。研究计划和方法：将在圣安东尼奥站点获取一部分受试者（来自大约 30 个家庭）的成像数据，以验证结构成像测量作为内表型。我们将在四年内每年为大约 60 名受试者（15 名患有 BPI 的兄弟姐妹、30 名未受影响的兄弟姐妹和 15 名对照者）获取 MRI。我们在为 BP 受试者和对照组获取这些 MRI 方面拥有丰富的经验，并且在过去两年中已为 140 名受试者进行了此类操作。我们将使用位于 UTHSCSA 研究成像中心 (RIC) 的 GE/Elscint Prestige 2-T 高场磁共振 (MR) 扫描仪。扫描将由训练有素的 MR 技术人员进行。首先获得矢状面侦察系列，以验证患者位置、图像质量和侧脑导水管整个范围的清晰度，以定位中线矢状面图像。 3D T1-FFE（T-1 加权快速场回波）将在冠状面进行，TR 为 25 ms，TE 为 5 ms，翻转角 40o，视场 (FOV) 240 mm x 220 mm，切片厚度1.0 mm，NEX=2，矩阵大小为256x192，获得覆盖整个大脑的图像。我们还将使用自旋回波序列来获取轴向平面上的 T2 和质子密度图像，并筛查神经放射学异常。收集 3D T1-FFE 和自旋回波序列的总时间约为 25 分钟。将根据先前发布的对这些特定大脑区域进行解剖 MRI 测量的方法来识别和描绘拟议的感兴趣区域 (ROI)。将参考标准解剖脑图册在 3 个解剖平面中识别解剖区域，并且将使用这些结构的三维体积渲染视图的检查来促进边界的识别。所有形态测量都将在 Jair Soares 博士的实验室中由经过良好培训的评估者进行这些特定程序，并且这些特定测量的评估者间可靠性超过 0.90。将使用 3D T1-FFE MRI 数据和基于生成灰质、白质和脑脊液像素直方图的半自动分割方法来估计大脑 ROI 中灰质、白质和脑脊液 (CSF) 的体积强度。该方法使用直方图方法来确定灰质、白质和脑脊液分离的阈值，按照先前描述的方法180,181186,187。根据建议的 60 名受影响个体和 60 名健康对照受试者的样本量，我们将有 80% 的功效 (1-b%) 拒绝组间无差异的零假设 (a=0.05)，以与较小的效应量进行对比 (最小效应量 = 0.25)。鉴于上面报告的前扣带回（效应大小 = 1.08）和左杏仁核（效应大小 = 0.64）的病例对照对比的效应大小，我们预计检测组间差异的能力在 96% 到 99.9% 之间变化。假设未受影响的亲属的体积测量值介于受影响和无关个体之间，有 120 名未受影响的家庭成员和 60 名健康对照受试者，我们预计检测组间差异的能力在 59% 到 99.6% 之间，具体取决于 ROI。