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
- 来源:
- 关键词:AccountingActivities of Daily LivingAdmixtureAge-YearsArthritisDataDegenerative polyarthritisDiagnosisDiseaseDisease ProgressionEthnic groupFailureGeneral PopulationGeneticGoalsHabilitationHealth Care CostsHealthcare SystemsHeritabilityHeterogeneityHip region structureHospitalizationIncidenceIndividualKneeLife StyleMediatingMeta-AnalysisOperative Surgical ProceduresOutcomePainParticipantPhenotypePrevalencePublic HealthRecording of previous eventsRecoveryRehabilitation therapyReplacement ArthroplastyResourcesSurveysTestingTraumatic ArthropathyTreatment CostVariantVeteransbiobankcohortcommon symptomcomorbiditydisabilityend stage diseaseexperiencegenetic informationgenetic predictorsgenetic variantgenome wide association studyhealth care service utilizationhealth related quality of lifehip replacement arthroplastyimproved mobilityknee replacement arthroplastymulti-ethnicpatient orientedprimary outcomeprognosticprogramsrecruitrehabilitation strategyresponsesecondary analysissecondary outcomesuccesstargeted treatment
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)的社会和以患者为中心的影响-包括
很大一部分人患有创伤后关节炎-影响深远:(一)退伍军人事务部的保健费用,
治疗每年超过8.8亿美元;(ii)VA医疗保健系统中约30%的退伍军人患有OA,
一个显着高于一般人群的比率;(iii)每年,10,000退伍军人与终末期关节炎
接受全髋关节(n~3500)或膝关节(n~6500)关节置换术(THA/TKA)和后续康复;(iv)
接受THA/TKA的退伍军人在健康相关生活质量(HRQL)方面存在严重缺陷,
日常生活活动(ADL)功能受限,医疗保健利用增加,
合并症和住院治疗;和(v)术后2-5年中重度功能限制的发生率
尽管进行了规定的康复治疗,但THA后手术率为30-35%,TKA后手术率为46-50%。OA有很强的遗传性
遗传率估计值> 30%。疼痛是最常见的症状,导致残疾,
降低HRQL。THA/TKA术后活动受限和疼痛的主要表型预测因子是
识别。然而,OA进展和THA/TKA成功恢复的遗传预测因子是,
还不知道这一发现将推动在术前和术后精确测量的进展。
退伍军人的康复。我们寻求利用丰富的MVP资源来测试总体
假设遗传变异解释了OA患病率、进展至终末期的有意义的比例
导致THA/TKA的疾病和恢复成功。将以三个具体目标来检验这一假设。
目的1:鉴定与OA相关的遗传变异。我们将在292,516名MVP参与者中执行GWAS
40-80岁-其中90,000人携带OA诊断-努力复制已知并识别新的
与OA相关的遗传变异和区域。作为二次分析,我们将执行GWAS以识别
3,696名创伤后关节炎退伍军人中与OA相关的遗传变异。我们将尝试
使用英国生物库中392,304人的数据复制了重要的发现,其中41,217人患有OA。
目的2:确定THA/TKA所示进展为终末期OA的遗传变异预后。我们
将在90,000名患有OA的MVP参与者中进行GWAS,以识别与达到
终末期(即THA/TKA)。在诊断为OA的这一队列中,我们将鉴定出OA患者特有的遗传变异。
进展至终末期的亚群-即7,600例接受THA或
OA诊断后的TKA。作为二次分析,我们将进行GWAS以识别遗传变异
与初次THA/TKA后5年内的翻修手术相关,这表明独特的遗传变异,
可能使一些退伍军人对初次THA/TKA的适应性较差。我们将复制重要的发现
使用英国生物样本库中13,071例THA和12,794例TKA的数据。探索性目的:识别遗传变异
通过活动受限(主要结局)、疼痛和HRQL(次要结局)定义THA/TKA恢复的预后
成果)。我们将在7,600名既往THA/TKA的MVP参与者中进行GWAS,以识别变体
与MVP基线和生活方式调查答复所示的恢复成功或失败相关。作为
二次分析,我们将调查康复是否介导遗传之间的关系,
变体和THA/TKA恢复。我们将使用两种策略最大限度地提高异质性:(i)通过执行GWAS
在每个主要的种族群体独立,并结合结果,使用荟萃分析占跨-
种族混合;和(ii)通过分析整个MVP队列进行多种族GWAS。最终
目的是确定OA的遗传变异预后以及OA和THA/TKA结局不良,
有针对性的、精确的术前和术后康复策略,改善移动功能,
HRQL和退伍军人的医疗保健利用率。
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)
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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:
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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
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9981438 - 财政年份:2016
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10179468 - 财政年份:2016
- 资助金额:
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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
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