Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder

酒精使用障碍和创伤后应激障碍的遗传和学习机制重叠

基本信息

  • 批准号:
    10155378
  • 负责人:
  • 金额:
    $ 16.52万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-05-01 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are common outcomes following trauma that are frequently comorbid, and this comorbidity is associated with greater symptom severity and poorer prognosis. Thus, efforts to better understand the etiology of these conditions is important for decreasing negative outcomes and improving prevention and treatment efforts, as much is still unknown regarding the etiology and mechanisms involved in their co-occurrence. Recent research has found that in addition to both phenotypes being moderately heritable, there is a modest degree of overlap in their latent genetic risk. Moreover, there is reason to suggest that fear-learning mechanisms frequently associated with PTSD may also be associated with AUD. Areas in need of further research include identification of molecular variation responsible for AUD/PTSD comorbidity, and extension of fear-learning models to AUD and comorbid AUD/PTSD populations. Developments in statistical procedures have afforded the ability to leverage genome- wide association data to answer key questions about these shared molecular underpinnings. The overarching goals of this K01 proposal are threefold. First, the study aims to use existing large-scale genome-wide data from the Psychiatric Genomics Consortium (PGC; PTSD and Substance Use Disorders workgroups) to examine the molecular overlap via bivariate single nucleotide polymorphism (SNP)-based heritability models, and determine if the polygenic risk score (PRS) from each disorder predicts case status in the other dataset. Second, a clinical laboratory study will be conducted using fear-conditioning paradigms in a trauma-exposed sample of diagnosis free controls, AUD, PTSD, and comorbid AUD/PTSD diagnostic groups to determine if deficits in learning are shared. Finally, an exploratory aim will use the PRS scores from the PGC data to generate risk scores in the lab sample to examine if there is a genetic association with conditioning deficits. To achieve these aims, the candidate and multidisciplinary mentorship team have developed a comprehensive training plan that delineates a series of training and research goals. These goals will incorporate training in the epidemiology and genetics of AUD and PTSD, molecular and statistical genetics techniques, and conduct of clinical laboratory paradigms using genetic and psychophysiological measures. This training and resultant findings will capitalize on existing expertise and provide additional, focused training to allow for the development of a multimodal research program that uses large-scale genetic association findings to develop mechanism-focused laboratory studies that inform upon the development and maintenance of this complex presentation. The proposed research represents an important contribution towards advancing our understanding of the complicated and frequently comorbid phenotypes of AUD and PTSD. The institutional environment is ideal for the candidate's goal of developing an independent research line that ultimately aims to decrease the burden of alcohol-related problems, consistent with NIAAA research priority.
项目概要 酒精使用障碍 (AUD) 和创伤后应激障碍 (PTSD) 是以下常见结果 经常合并症的创伤,并且这种合并症与更严重的症状相关 预后较差。因此,努力更好地了解这些病症的病因对于减少 负面结果并改善预防和治疗工作,因为关于该问题仍存在很多未知数 它们同时发生的病因和机制。最近的研究发现,除了两者 表型具有中等遗传性,因此它们的潜在遗传风险存在一定程度的重叠。 此外,有理由表明,经常与 PTSD 相关的恐惧学习机制也可能 与澳元相关。需要进一步研究的领域包括分子变异的识别 负责 AUD/PTSD 合并症,并将恐惧学习模型扩展到 AUD 和合并症 AUD/PTSD 人群。统计程序的发展提供了利用基因组的能力 广泛的关联数据可以回答有关这些共享分子基础的关键问题。首要的 K01 提案的目标有三个。首先,该研究旨在利用现有的大规模全基因组数据 来自精神病基因组学联盟(PGC;PTSD 和药物使用障碍工作组) 通过基于双变量单核苷酸多态性 (SNP) 的遗传力模型检查分子重叠, 并确定每种疾病的多基因风险评分 (PRS) 是否可以预测其他数据集中的病例状态。 其次,将使用恐惧调节范式在遭受创伤的患者中进行临床实验室研究。 无诊断对照、AUD、PTSD 和共病 AUD/PTSD 诊断组样本,以确定是否 学习上的缺陷是共同的。最后,探索性目标将使用 PGC 数据中的 PRS 分数来 在实验室样本中生成风险评分,以检查是否与条件缺陷存在遗传关联。 为了实现这些目标,候选人和多学科指导团队制定了 全面的培训计划,描绘了一系列的培训和研究目标。这些目标将 纳入 AUD 和 PTSD 的流行病学和遗传学、分子和统计遗传学方面的培训 技术,以及使用遗传和心理生理学措施进行临床实验室范例。 该培训和由此产生的结果将利用现有的专业知识并提供额外的、有针对性的培训 允许开发使用大规模遗传关联的多模式研究计划 开展以机制为重点的实验室研究的发现,为开发和维护提供信息 这个复杂的演示。拟议的研究对推进 我们对 AUD 和 PTSD 复杂且常见的共病表型的理解。机构 环境对于候选人发展独立研究线的目标来说是理想的,最终旨在 减轻酒精相关问题的负担,符合 NIAAA 的研究重点。

项目成果

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Christina M Sheerin其他文献

Christina M Sheerin的其他文献

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{{ truncateString('Christina M Sheerin', 18)}}的其他基金

Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder
酒精使用障碍和创伤后应激障碍的遗传和学习机制重叠
  • 批准号:
    9920643
  • 财政年份:
    2018
  • 资助金额:
    $ 16.52万
  • 项目类别:
Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder
酒精使用障碍和创伤后应激障碍的遗传和学习机制重叠
  • 批准号:
    9445540
  • 财政年份:
    2018
  • 资助金额:
    $ 16.52万
  • 项目类别:
Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder
酒精使用障碍和创伤后应激障碍的遗传和学习机制重叠
  • 批准号:
    10393749
  • 财政年份:
    2018
  • 资助金额:
    $ 16.52万
  • 项目类别:
Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder
酒精使用障碍和创伤后应激障碍的遗传和学习机制重叠
  • 批准号:
    10392417
  • 财政年份:
    2018
  • 资助金额:
    $ 16.52万
  • 项目类别:
Functional relations between alcohol use and mental/physical health in the wake of the COVID-19 pandemic
COVID-19 大流行后饮酒与心理/身体健康之间的功能关系
  • 批准号:
    10203554
  • 财政年份:
    2018
  • 资助金额:
    $ 16.52万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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