Translational Approach to Studying miRNA functions in sACC and amygdala in patients with BPD

研究 BPD 患者 sACC 和杏仁核 miRNA 功能的转化方法

基本信息

  • 批准号:
    10635583
  • 负责人:
  • 金额:
    $ 63.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-05-01 至 2028-02-29
  • 项目状态:
    未结题

项目摘要

Abstract: Bipolar disorder (BPD) is a severe mental disorder with a significant burden on public health. MiRNAs are highly expressed in the brain and have been shown by us and others to play a role in the neuropathology of BPD and other psychiatric disorders. However, to date, all published postmortem brain miRNA expression studies of BPD have been hampered by small sample sizes, older detection platforms, and a lack of comprehensive data integration with other genomic resources. To address these limitations, we propose a translational approach that will apply miRNA sequencing in the amygdala and subgenual cingulate anterior cortex (sAAC) in 150 patients diagnosed with bipolar disorder and matched 150 neurotypical controls, followed by a replication study in an independent sample of 100 matched case/control sample. Our aims are designed to take full advantage of this large and exceptionally well clinically characterized sample. With our large discovery and replication samples, we are powered to identify moderate to small effect sizes typically observed in neuropsychiatric disorders. By leveraging other pre-existing genomic datasets (i.e., GWAS data and RNA-seq) generated in our sample, we will apply a state-of-art series of bioinformatic and statistical approaches for the comprehensive integration of these genomic data. This integration will lead to the generation of specific and testable hypotheses. As an example, integrating the miRNA- seq data with GWAS of BPD (from the Psychiatric Genomics Consortium) will reveal the genetic mechanisms by which genome-wide significant risk variants contribute to the etiology of bipolar disorder, e.g., variants affecting miRNA expression between BPD cases and controls. Integrating the miRNA-Seq and RNA-Seq data will identify miRNA gene targets with important functions in the etiology of bipolar disorder. Finally, we will identify a set of high confidence risk miRNA of BPD (i.e., miRNAs with convergent evidence from the discovery, eQTL, bioinformatic, and replication analyses) and deliver these in mice models to delineate the disease-specific functions and roles these miRNA play in BPD neuropathology. In summary, the neurobiological mechanisms by which polymorphisms associated with BPD increase the risk for bipolar disorder are unknown. We hypothesize that one of the mechanisms contributing to the neuropathology of BPD is the ability of risk BPD variants to affect miRNA expression. Using such large discovery and replication brain samples of BPD, we will identify miRNA, whose expression is robustly associated with bipolar disorder and under the control of risk variants for BPD and further validate their disease functions by testing their impact on behavioral measures in mice models.
摘要: 双相情感障碍(BPD)是一种严重的精神障碍,对公共卫生造成重大负担。mirna是 在大脑中高度表达,并且已经被我们和其他人证明在BPD的神经病理学中发挥作用 和其他精神疾病。然而,到目前为止,所有已发表的死后脑miRNA表达研究, BPD受到样本量小、检测平台较旧以及缺乏全面数据的阻碍 与其他基因资源的整合。 为了解决这些局限性,我们提出了一种翻译方法,将miRNA测序应用于 杏仁核和膝下扣带前皮质(sAAC)的150例诊断为双相情感障碍, 匹配150个神经典型对照,然后在100个匹配的独立样本中进行重复研究。 病例/对照样本。我们的目标是充分利用这一巨大的和非常好的临床 特征样品。凭借我们的大规模发现和复制样本,我们有能力识别中度至 在神经精神疾病中通常观察到的小效应量。通过利用其他现有的基因组 数据集(即,GWAS数据和RNA-seq),我们将应用一系列最先进的 生物信息学和统计学方法用于这些基因组数据的全面整合。这 整合将导致产生具体且可测试的假设。例如,整合miRNA- BPD的GWAS(来自精神病基因组学联盟)的seq数据将揭示遗传机制 全基因组显著的风险变异体通过其促成双相情感障碍的病因学,例如,变体 影响BPD病例和对照之间的miRNA表达。整合miRNA-Seq和RNA-Seq数据 将确定在双相情感障碍病因学中具有重要功能的miRNA基因靶点。最后,我们将确定 一组BPD的高置信风险miRNA(即,miRNAs与eQTL的发现, 生物信息学和复制分析),并在小鼠模型中递送这些,以描绘疾病特异性 这些miRNA在BPD神经病理学中发挥的功能和作用。 总之,与BPD相关的多态性增加风险的神经生物学机制 双相情感障碍的治疗方法尚不清楚。我们假设导致神经病理学的机制之一 BPD风险变异体影响miRNA表达的能力。使用如此大的发现和复制 BPD的大脑样本,我们将鉴定miRNA,其表达与双相情感障碍密切相关, 在BPD风险变异的控制下,通过测试它们对BPD的影响, 小鼠模型中的行为测量。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Vladimir Ivanov Vladimirov其他文献

Vladimir Ivanov Vladimirov的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Vladimir Ivanov Vladimirov', 18)}}的其他基金

Assessing miRNA expression in the Corticolimbic System of Major Depressive Disorder
评估重度抑郁症皮质边缘系统中的 miRNA 表达
  • 批准号:
    10810045
  • 财政年份:
    2019
  • 资助金额:
    $ 63.15万
  • 项目类别:
Assessing miRNA expression in the Corticolimbic System of Major Depressive Disorder
评估重度抑郁症皮质边缘系统中的 miRNA 表达
  • 批准号:
    9904778
  • 财政年份:
    2019
  • 资助金额:
    $ 63.15万
  • 项目类别:
Assessing miRNA expression in the Corticolimbic System of Major Depressive Disorder
评估重度抑郁症皮质边缘系统中的 miRNA 表达
  • 批准号:
    9761634
  • 财政年份:
    2019
  • 资助金额:
    $ 63.15万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 63.15万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了