A2CPS Genetic Variant Core

A2CPS 遗传变异核心

• 批准号: 10000902
• 负责人: KELLY A FRAZER
• 金额: $ 20.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000902
• 关键词: Acute; Acute Pain; Adherence; Biological Markers; Blood specimen; Clinical; Clinical Data; Collaborations; Collection; Communication; Complex; DNA; Data; Data Analyses; Data Coordinating Center; Data Set; Deposition; Development; Ensure; Generations; Genetic; Genomic medicine; Goals; Human Resources; Individual; Institutes; Knowledge; Longitudinal cohort; Metadata; Methods; Molecular; Multiomic Data; Musculoskeletal; Operative Surgical Procedures; Pain; Participant; Patients; Persons; Phenotype; Predisposition; Prevention strategy; Procedures; Process; Protocols documentation; Quality Control; Reporting; Reproducibility; Research Design; Research Personnel; Resistance; Resources; Sampling; Trauma; Validation; Variant; Work; biomarker selection; candidate marker; candidate selection; chronic pain; clinical center; data analysis pipeline; data integration; data standards; data submission; experience; genetic association; genetic predictors; genetic selection; genetic signature; genetic variant; genomic locus; imaging biomarker; meetings; novel; personalized strategies; primary outcome; programs; psychosocial; recruit; resilience; sample collection; screening; sex; skills; variant detection

GENETIC VARIANT CORE SUMMARY Chronic pain is a complex problem, likely influenced by multiple environmental and genetic factors. Growing evidence for a genetic basis for developing chronic pain suggests it may be possible to use genetic predictors to differentiate between patients likely to be susceptible versus resilient to the development of chronic pain. This project is the Genetic Variant Core (GVC) of the Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program. In this Program, the Clinical Centers will recruit and collect clinical data and biofluid samples from two longitudinal cohorts of 1800 subjects each. Biofluid samples will be collected 0, 3, and 6 months after an acute pain episode, consisting of a specific surgical procedure or a specific musculoskeletal trauma. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers. For the proposed Genetic Variant Core, Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Program to establish the final study design and protocols. All of the A2CPS Program investigators will work together to establish the 40 primary outcome biomarkers. The ODGC and Clinical Center investigators will jointly decide on the specific sample type(s) and collection/processing/storage methods. The ODGC and Data integration Resource Center/Data Coordination Component (DIRC/DCC) investigators will establish Metadata and Data Standards and a workflow for submission of metadata and data to the DCC. The GVC and the Administrative Core of the ODGC will establish an integrated LIMS for sample and data tracking, and recording of metadata. The GVC and DIRC/Data Integration and Analysis Component (DIAC) will establish data analysis pipelines. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on DNA isolation and genetic variant arrays for the 3600 participant samples that will be collected by the Clinical Centers. Aim 3 will encompass submission of metadata and data to the DIRC/DCC, quality control of the data, and data analysis and interpretation. The primary goal of this Component is generation and submission of high-quality gene variant array data for the validation of pre-selected genetic variant biomarkers. While the study is not powered to identify novel genetic associations, we expect to extend the analysis beyond the jointly selected genetic variant biomarkers to include additional variants implicated in susceptibility/resilience to chronic pain. GVC component investigators will participate in integrative analyses with the DIRC/DIAC aimed at developing pain signatures comprised of multiple biomarker types (including molecular, clinical, psychosocial, and/or imaging biomarkers) indicating susceptibility/resilience to chronic pain, which can be used to develop personalized strategies for prevention and treatment of chronic pain. The personnel for this proposed GVC have acquired the necessary skills and knowledge to successfully execute this project from participation in multiple large-scale projects generating genetic variant array data.

遗传变异核心 概括 慢性疼痛是一个复杂的问题，可能受到多种环境和遗传因素的影响。生长 慢性疼痛存在遗传基础的证据表明，利用遗传预测因子来预测慢性疼痛是可能的。 区分可能对慢性疼痛发展敏感的患者和对慢性疼痛有抵抗力的患者。这 项目是组学数据生成中心 (ODGC) 的遗传变异核心 (GVC)，用于急性到慢性疾病 疼痛特征 (A2CPS) 计划。在该计划中，临床中心将招募和收集临床数据并 生物体液样本来自两个纵向队列，每个队列有 1800 名受试者。生物流体样本将在 0、3 和 急性疼痛发作后 6 个月，包括特定的外科手术或特定的肌肉骨骼 创伤。这些样本将用于生成多组学数据，以验证 40 种主要结果生物标志物 表明对慢性疼痛发展的易感性或恢复力，以及确定新的候选者 生物标志物。对于拟议的遗传变异核心，目标 1 将在第一年执行，将涉及密切 与 A2CPS 计划的其他组成部分合作，确定最终的研究设计和方案。全部 A2CPS 计划的研究人员将共同努力建立 40 个主要结果生物标志物。这 ODGC 和临床中心研究人员将共同决定具体样本类型和 收集/处理/存储方法。 ODGC 和数据集成资源中心/数据协调 组件（DIRC/DCC）研究人员将建立元数据和数据标准以及工作流程 向 DCC 提交元数据和数据。 GVC 和 ODGC 的行政核心将建立 用于样品和数据跟踪以及元数据记录的集成 LIMS。 GVC 和 DIRC/数据 集成和分析组件（DIAC）将建立数据分析管道。目标 2 和 3 将持续数年 2-4，目标 2 重点关注 3600 个参与者样本的 DNA 分离和遗传变异阵列，这些样本将被 由临床中心收集。目标 3 将包括向 DIRC/DCC 提交元数据和数据， 数据质量控制以及数据分析和解释。该组件的主要目标是生成 并提交高质量的基因变异阵列数据以验证预选的遗传变异 生物标志物。虽然这项研究并不能确定新的遗传关联，但我们希望能够扩大研究范围 除了联合选择的遗传变异生物标志物之外，分析还包括与 对慢性疼痛的敏感性/抵抗力。 GVC 组成部分的研究人员将参与综合分析 DIRC/DIAC 旨在开发由多种生物标志物类型（包括分子、 临床、社会心理和/或影像生物标志物）表明对慢性疼痛的易感性/恢复力，这可以 用于制定预防和治疗慢性疼痛的个性化策略。本次活动人员 拟议的 GVC 已获得成功执行该项目所需的技能和知识 参与多个生成遗传变异阵列数据的大型项目。