BIPOLAR ENDOPHENOTYPES IN POPULATION ISOLATES

群体分离株中的双极内表型

• 批准号: 8171081
• 负责人: NELSON B. FREIMER
• 金额: $ 1.22万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171081
• 关键词: Affect; Alleles; Bipolar Disorder; Brain scan; Circadian Rhythms; Clinical; Colombia; Computer Retrieval of Information on Scientific Projects Database; Costa Rica; Functional disorder; Funding; Future; Genetic; Genotype; Grant; Heritable Quantitative Trait; Individual; Institution; Light; Magnetic Resonance Imaging; Maps; Measures; Neurocognition; Neurocognitive; Population; Population Study; Probability; Quantitative Trait Loci; Research; Research Personnel; Resolution; Resources; Series; Single Nucleotide Polymorphism; Source; Temperament; United States National Institutes of Health; Variant; base; clinical phenotype; endophenotype; experience; genetic pedigree; genome-wide; member; tool

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. This proposal is to identify heritable, quantitative traits (endophenotypes) that are related to bipolar disorder (BP) and then to use these endophenotypes for linkage and association analyses to identify quantitative trait loci (QTL) in a series of well characterized extended pedigrees. It is hypothesized that the endophenotypes may be more powerfully genetically mapped than the clinical phenotype. The first step is to measure selected neuroanatomical, neurocognitive, temperament, and activity related features previously shown or hypothesized to be associated with BP. These features will be measured using high resolution structural magnetic resonance imaging (MRI) brain scans, and widely used scales for neurocognition, temperament, and seasonal/circadian variation in activity. The investigative team has considerable experience in using these assessment tools. Aggregation of each of these features will be assessed in about 400 members of 11 previously investigated extended pedigrees from the genetically isolated populations of Antioquia (Colombia) and Costa Rica. These pedigrees were ascertained based on their including multiple individuals affected with severe BP (BP-I). Therefore, these pedigrees should be enriched for the presence of BP-associated alleles for the previous endophenotypic features. Any of the endophenotypes that demonstrate familial aggregation will be used for genomewide QTL linkage and association analysis of the complete pedigrees using high-resolution genomewide genotypes (for single nucleotide polymorphisms, SNP's) that we will obtain in this project. The study will take advantage of the well-characterized pedigrees and extensive genealogical and clinical characterization already undertaken by members of the collaborative team on these pedigrees. The genetic homogeneity of the two study populations should enhance the probability that this project will identify QTL associated with BP. Future studies will use the QTL to identify sequence variants that may shed light on the pathophysiology of BP.

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。 该建议是为了确定与双相情感障碍（BP）相关的可遗传性，定量性状（内表型），然后将这些末端表型用于连锁和关联分析，以识别一系列表征良好的扩展分子的定量性状基因座（QTL）。假设与临床表型相比，遗传映射可能更有力地映射。第一步是测量选定的神经解剖学，神经认知，气质和与活动相关的特征，以前显示或假设与BP相关。这些特征将使用高分辨率的结构磁共振成像（MRI）脑扫描来测量，并广泛使用用于神经认知，气质和季节性/昼夜节律活动的量表。调查团队在使用这些评估工具方面具有丰富的经验。 这些特征的汇总将在先前研究的11个延长的血统中的大约400名中，从抗Quia（哥伦比亚）和哥斯达黎加（Costa Rica）中进行的11名成员进行评估。这些血统基于它们的包括严重BP（BP-I）的多个个体确定。因此，对于以前的内型特征，应将这些谱系富集以富集与BP相关的等位基因的存在。任何证明家族聚集的内表型都将用于全基因组QTL链接和使用高分辨率全基因组基因型（用于单核苷酸多态性，SNP）对完整的谱系的关联分析，我们将在该项目中获得。这项研究将利用特征良好的血统和合作团队成员在这些谱系上已经进行的广泛的家谱和临床表征。这两个研究人群的遗传同质性应提高该项目识别与BP相关的QTL的可能性。未来的研究将使用QTL来识别可能阐明BP病理生理的序列变体。