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

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2020 · —

## Abstract

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 findi...

## Key facts

- **NIH application ID:** 10174848
- **Project number:** 5I01RX002745-03
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** Jasvinder Singh
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174848

## Citation

> US National Institutes of Health, RePORTER application 10174848, Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation (5I01RX002745-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174848. Licensed CC0.

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