medwireNews: Polygenic risk scores (PRSs) for advanced knee and hip osteoarthritis (OA) are significantly associated with the likelihood of requiring joint replacement in community-dwelling older adults, Australian study findings indicate.
The research suggests that “PRSs have the potential to improve prevention of severe knee and hip osteoarthritis by providing a personalized approach and identifying individuals who may benefit from early intervention,” write Flavia Cicuttini (Monash University, Melbourne, Victoria) and co-authors in Arthritis & Rheumatology.
Cicuttini and team calculated knee- and hip-specific PRSs, derived from a recent genome-wide association study meta-analysis, for 12,093 individuals of European genetic descent aged 70–79 years (mean 75 years) who were participating in the ASPREE trial. The PRS for total knee replacement (TKR) included 10 single nucleotide polymorphisms (SNPs) while that for total hip replacement (THR) included 37 SNPs.
Overall, 11.8% of participants underwent TKR and 10.7% had a THR either during the trial (median follow-up 4.7 years) or prior to enrolment.
The researchers found that the proportion of patients who underwent TKR increased with increasing PRS risk group, from 9.5% in the low-risk (quintile 1) group to 11.9% in the medium-risk (quintiles 2–4) group and 13.5% in the high-risk (quintile 5) group.
After adjustment for age, sex, BMI, and socioeconomic status, each standard deviation (SD) increase in PRS was associated with a significant 13% increase in the risk for TKR.
In addition, the likelihood of TKR was a significant 1.30-fold higher in the medium PRS group relative to the low PRS group, and a significant 1.44-fold higher in the high PRS group.
The team observed similar results for THR. In this case, each SD increase in PRS was associated with a significant 23% increase in the risk for THR, and individuals in the medium and high PRS groups were a significant 1.27 and 1.88 times more likely to have THR than those in the low PRS group, respectively.
Cicuttini et al note that results did not differ significantly when they analyzed incident and prevalent joint replacements separately, but there was an interaction between PRS and sex for THR. In this case, the likelihood of hip replacement was a significant 2.19-fold higher in the high versus low PRS group in women and a significant 1.57-fold higher in men.
“Our study represents an important step in the assessment of genomic risk scores for prediction of advanced OA in older adults, where the burden of disease is high,” the authors remark.
They add: “Access to information on genetic risk, prior to the manifestation of clinical symptoms, has the potential to improve compliance with preventive strategies and address risk factors earlier in the disease course. Genetic risk scores for OA therefore have the potential to be incorporated into decision support algorithms earlier in life, to improve targeting of interventions and clinical management.”
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