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

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2023 · —

## Abstract

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.

## Key facts

- **NIH application ID:** 10643606
- **Project number:** 2I01RX002745-06
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** Merry-Lynn Noelle McDonald Donnelly
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2023-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10643606

## Citation

> US National Institutes of Health, RePORTER application 10643606, Genetics of Osteoarthritis and Joint Replacement Recovery: Key to Precision Rehabilitation (2I01RX002745-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10643606. Licensed CC0.

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