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：
7718754
负责人：
Michael A Escamilla
金额：
$ 0.04万
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：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7718754
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 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. 2007 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 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 180,181,186,187. 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.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。 2007 目的：该项目的目的是收集来自385个拉丁裔血统家族的诊断信息和DNA样本，每个家族至少有两个受BPI（DSM-IV诊断）影响的兄弟姐妹，以检测该人群中BPI敏感性基因座。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。研究计划和方法：将为San Antonio站点的受试者（大约30个家庭）的子集获取成像数据，以验证结构成像措施作为内型型。我们将在四年内每年获得大约60名受试者的MRI（BPI 15个兄弟姐妹，30个未受影响的兄弟姐妹和15个对照）。我们在获得BP受试者和对照组的这些MRI方面有丰富的经验，并且在过去两年中为140名受试者做到了这一点。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技术人员进行。首先获得了矢状侦察兵系列，以验证Sylvius渡槽范围的患者位置，图像质量和清晰度，以找到中线矢状图像。 3D T1-FFE（T-1加权快速磁场回波）将在冠状平面上进行25毫秒，TE为5 ms，40O的翻转角度（FOV）240 mm x 220 mm，切片厚度为1.0 mm，Nex = 2，nex = 2和Matrix大小为256X192，以获得整个脑材的图像。我们还将使用自旋回波序列在轴向平面和神经放射异常的筛选中获得T2和质子密度图像。收集3D T1-FFE和自旋回波序列的总时间约为25分钟。拟议的利益区域（ROI）将根据先前发表的这些特定大脑区域的解剖学MRI测量方法来识别和描述。关于标准的解剖脑图集，将在3个解剖平面中鉴定解剖区域，并检查这些结构的三维体积渲染视图的检查将用于促进边界的识别。所有形态计量指标将由经过良好培训的评分者执行这些特定程序，并针对这些特定测量结果实现了0.90以上的评估者可靠性。将使用3D T1-FFE MRI数据和一种基于灰色，白质和脑脊液脑脊髓流体像素强度的直方图，使用3D T1-FFE MRI数据和半自动分割方法估算脑ROI中的灰质和白质和脑脊液（CSF）的体积。根据先前描述的方法，该方法使用直方图方法来确定灰质，白质和CSF分离的阈值180,181,186,187。提出的样本量为60个受影响的个体和60个健康比较受试者，我们将拥有80％的功率（1-b％），以拒绝群体差异之间无效的假设（a = 0.05），与较小的效应尺寸（最小效应尺寸= 0.25）之间的群体差异之间拒绝了。鉴于上扣带回（效应= 1.08）和左杏仁核（效应尺寸= 0.64）的病例对照对比的效应大小，我们预计在组差异之间的功率从96％到99.9％。假设未受影响的亲属的体积测量是受影响和无关的个体之间的中途，有120个未受影响的家庭成员和60个健康比较受试者，我们预计会在群体差异之间检测到59％至99.6％的范围，具体取决于ROI。