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:
    10535425
  • 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:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

The societal and patient-centered impacts of end-stage osteoarthritis (OA) among Veterans – including a significant proportion suffering from post-traumatic arthritis – are profound: (i) VA healthcare costs for treatment exceed $880 million annually; (ii) ~30% of Veterans in the VA healthcare system have OA, which is a significantly higher rate than the general population; (iii) each year, 10,000 Veterans with end-stage arthritis undergo total hip (n~3500) or knee (n~6500) arthroplasty (THA/TKA) and subsequent rehabilitation; (iv) Veterans who undergo THA/TKA experience profound deficits in health-related quality of life (HRQL), severe functional limitations in activities of daily living (ADL), increased healthcare utilization, and higher incidence of comorbidities and hospitalization; and (v) incidence of moderate-severe functional limitations 2-5 years post- surgery is 30-35% post-THA and 46-50% post-TKA despite prescribed rehabilitation. OA has a strong genetic component with heritability estimates >30%. Pain is the most common symptom, contributing to disability and decreased HRQL. Major phenotypic predictors of post-THA/TKA mobility limitation and pain have been identifed. However, genetic predictors of both the progression of OA and success of THA/TKA recovery are as yet unknown. Such discovery would fuel progress toward precision pre-habilitation and post-surgical rehabilitation among Veterans. We seek to leverage the rich MVP resource to test the overarching hypothesis that genetic variants explain a meaningful proportion of OA prevalence, progression to end-stage disease leading to THA/TKA, and recovery success. This hypothesis will be tested with three specific aims. Aim 1: To identify genetic variants associated with OA. We will perform GWAS in 292,516 MVP participants 40-80 years of age – of which 90,000 carry an OA diagnosis – in an effort to replicate known and identify new genetic variants and regions associated with OA. As a secondary analysis, we will perform GWAS to identify genetic variants associated with OA among 3,696 Veterans with post-traumatic arthritis. We will attempt to replicate significant findings using data on 392,304 individuals in the UK Biobank, of which 41,217 have OA. Aim 2: To identify genetic variants prognostic of progression to end-stage OA, as indicated by THA/TKA. We will perform GWAS in the 90,000 MVP participants with OA to identify variants associated with reaching the end-stage (i.e. THA/TKA). Within this cohort with diagnosed OA, we will identify genetic variants unique to the subpopulation that progressed to end-stage – i.e. the 7,600 MVP participants who have undergone THA or TKA subsequent to OA diagnosis. As a secondary analysis, we will perform GWAS to identify genetic variants associated with revision surgery within 5 years of the initial THA/TKA, suggesting unique genetic variants that may predispose some Veterans to poor adaptations to the initial THA/TKA. We will replicate significant findings using data from 13,071 THA and 12,794 TKA in the UK Biobank. Exploratory Aim: To identify genetic variants prognostic of THA/TKA recovery defined by mobility limitation (primary outcome), pain, and HRQL (secondary outcomes). We will perform GWAS among the 7,600 MVP participants with past THA/TKA to identify variants associated with recovery success or failure, as indicated by MVP Baseline and Lifestyle survey responses. As a secondary analysis, we will investigate whether rehabilitation mediates the relationship between genetic variants and THA/TKA recovery. We will maximize heterogeneity using two strategies: (i) By performing GWAS in each major ethnic group independently and combining results using meta-analysis accounting for trans- ethnic admixture; and (ii) By analyzing the entire MVP cohort to perform a multi-ethnic GWAS. The ultimate goal is to identify genetic variants prognostic of OA as well as poor OA and THA/TKA outcomes to develop targeted, precision pre-habilitation and post-surgical rehabilitation strategies improving mobility function, HRQL, and healthcare utilization among Veterans.
退伍军人终末期骨关节炎(OA)的社会和患者为中心的影响-包括a

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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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:
    10643606
  • 财政年份:
    2023
  • 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:
    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:
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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