Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation

骨关节炎的遗传学和关节置换恢复:精准康复的关键

基本信息

  • 批准号:
    10643606
  • 负责人:
  • 金额:
    --
  • 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:
    2023-08-01 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

The societal and patient-centered impacts of end-stage osteoarthritis (OA) among United States Veterans are profound. More than 30% of Veterans in the VA healthcare system have OA which is significantly higher than in the general population. VA treatment costs for OA are high, exceeding $880 million annually. Still, apart from pain and symptom management and end stage surgical intervention, there are no effective therapeutic treatments for OA. Despite prescribed rehabilitation post-surgery, Veterans who undergo total hip arthroplasty (THA) or total knee arthroplasty (TKA) experience profound deficits in health-related quality of life (HRQL), severe limitations in activities of daily living, increased healthcare utilization, and higher incidence of comorbidities. OA has a strong genetic component with heritability estimates >30%. Our research in the Million Veteran Program (MVP) cohort led to discoveries in key areas. First, our ancestry specific and multi-ancestry analyses in over 477,000 MVP and the UK Biobank (UKB) participants identified of novel genetic regions associated with OA. Second, OA frequency was higher in the MVP than in our replication cohort (UKB) despite using identical electronic health record diagnosis codes which may have hampered replication efforts. Third, our research in the MVP cohort demonstrated a higher OA heritability in African American and Hispanic Veterans than those of European White descent. Our overall goal is to identify pre- and post-rehabilitative biomarkers to enhance physicians’ intuition for predicting patient prognosis for Veterans with OA and/or PTOA. Toward this goal and to fill important knowledge gaps regarding the association of genetic factors with OA and outcomes, in Aim 1, a) we will confirm genetic variants associated with OA prevalence and progression to end- stage OA as well as b) develop and evaluate the performance of a polygenic risk score (PRS) to identify Veterans at risk of progression to total hip/knee joint arthroplasty; in Aim 2, we will identify genetic variants prognostic of THA/TKA recovery; and in Aim 3, we will determine whether genetic variants associated with the development of post-traumatic OA (PTOA) are distinct from known genetic determinants of idiopathic OA. We will identify biomarkers to enable targeted, precision pre-habilitation and post-surgical rehabilitation strategies improving mobility function, HRQL, and healthcare utilization among Veterans with OA.
美国终末期骨关节炎的社会和以患者为中心的影响 退伍军人是有深度的。在退伍军人保健系统中,超过30%的退伍军人患有骨性关节炎,这是显着的 高于普通人群。退伍军人管理局治疗骨性关节炎的费用很高,每年超过8.8亿美元。不过, 除了疼痛和症状管理和终末期手术干预外,没有有效的治疗方法。 治疗骨性关节炎。尽管规定了术后康复,但接受全髋关节置换术的退伍军人 全膝关节置换术(THA)或全膝关节置换术(TKA)在健康相关的生活质量(HRQL)方面存在严重缺陷, 严重限制日常生活活动,提高医疗利用率,以及更高的发病率 合并症。骨质疏松症有很强的遗传成分,遗传力估计为30%。我们的研究以百万美元计 退伍军人计划(MVP)队列导致了关键领域的发现。第一,我们的祖先特定和多祖先 对477,000多名MVP和英国生物库(UKB)参与者的分析确定了新的基因区域 与办公自动化相关。其次,MVP中的OA频率高于我们的复制队列(UKB),尽管 使用相同的电子健康记录诊断代码,这可能阻碍了复制工作。第三, 我们在MVP队列中的研究表明,非裔美国人和西班牙裔退伍军人的骨性关节炎遗传率更高 而不是欧洲白人后裔。我们的总体目标是确定康复前后的生物标志物 目的:提高医生对退伍军人骨性关节炎和/或PTOA患者预后的预见性。 为了实现这一目标,并填补关于遗传因素与骨质疏松症和 结果,在目标1中,a)我们将确认与OA患病率和进展相关的基因变异- 阶段OA以及b)制定和评估多基因风险评分(PR)的表现,以识别退伍军人 有可能发展为全髋关节/膝关节置换术;在目标2中,我们将识别预测髋关节/膝关节置换预后的遗传变异。 THA/TKA恢复;在目标3,我们将确定基因变异是否与发育有关 创伤后骨性关节炎(PTOA)与特发性骨性关节炎的已知遗传决定因素不同。我们将确定 生物标志物,以实现有针对性的精确康复和手术后康复战略的改进 退伍军人骨关节炎患者的活动功能、HRQL和医疗保健利用。

项目成果

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Jasvinder A Singh其他文献

Consensus on the need for a hierarchical list of patient-reported pain outcomes for meta-analyses of knee osteoarthritis trials
  • DOI:
    10.1186/1745-6215-16-s1-p36
  • 发表时间:
    2015-05-29
  • 期刊:
  • 影响因子:
    2.000
  • 作者:
    Louise Klokker;Lara J Maxwell;Peter Juni;David Tovey;Paula R Williamson;Maarten Boers;Niti Goel;Rachelle Buchbinder;Lyn March;Caroline B Terwee;Jasvinder A Singh;Peter Tugwell;Robin Christensen
  • 通讯作者:
    Robin Christensen

Jasvinder A Singh的其他文献

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{{ truncateString('Jasvinder A Singh', 18)}}的其他基金

Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation
骨关节炎的遗传学和关节置换恢复:精准康复的关键
  • 批准号:
    10174848
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation
骨关节炎的遗传学和关节置换恢复:精准康复的关键
  • 批准号:
    10839541
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation
骨关节炎的遗传学和关节置换恢复:精准康复的关键
  • 批准号:
    10535425
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
STorytelling to Improve DiseasE outcomes in GoUT: The STRIDE-GO Study
讲故事可改善痛风的疾病结果:STRIDE-GO 研究
  • 批准号:
    10178095
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
STorytelling to Improve DiseasE outcomes in GoUT: The STRIDE-GO Study
讲故事可改善痛风的疾病结果:STRIDE-GO 研究
  • 批准号:
    9981438
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
STorytelling to Improve DiseasE outcomes in GoUT: The STRIDE-GO Study
讲故事可改善痛风的疾病结果:STRIDE-GO 研究
  • 批准号:
    10179468
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
STorytelling to Improve DiseasE outcomes in GoUT: The STRIDE-GO Study
讲故事可改善痛风的疾病结果:STRIDE-GO 研究
  • 批准号:
    9085817
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
SToRytelling to Improve DiseasE outcomes in Gout: The STRIDE-GO Study
讲故事可改善痛风疾病的结果:STRIDE-GO 研究
  • 批准号:
    8783912
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Project 4: Protecting Renal functiOn with Urate-lowering Drugs (PROUD)
项目4:用降尿酸药物保护肾功能(PROUD)
  • 批准号:
    10017010
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Project 4: Protecting Renal functiOn with Urate-lowering Drugs (PROUD)
项目4:用降尿酸药物保护肾功能(PROUD)
  • 批准号:
    10263207
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:

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