TY - JOUR
T1 - Risk Assessment for Hip and Knee Osteoarthritis Using Polygenic Risk Scores
AU - Sedaghati-Khayat, Bahar
AU - Boer, Cindy G.
AU - Runhaar, Jos
AU - Bierma-Zeinstra, Sita M.A.
AU - Broer, Linda
AU - Ikram, M. Arfan
AU - Zeggini, Eleftheria
AU - Uitterlinden, André G.
AU - van Rooij, Jeroen G.J.
AU - van Meurs, Joyce B.J.
N1 - © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2022/9
Y1 - 2022/9
N2 - Objective: Polygenic risk scores (PRS) allow risk stratification using common single-nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS. Methods: We analyzed 12,732 individuals from a population-based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high-risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome-wide association study meta-analysis. Standardized PRS (with Z transformation) were used in all analyses. Results: We found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1–1.5) and 1.6 (95% CI 1.3–1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1–1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8–1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4–3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution. Conclusion: Our findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS-based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.
AB - Objective: Polygenic risk scores (PRS) allow risk stratification using common single-nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS. Methods: We analyzed 12,732 individuals from a population-based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high-risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome-wide association study meta-analysis. Standardized PRS (with Z transformation) were used in all analyses. Results: We found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1–1.5) and 1.6 (95% CI 1.3–1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1–1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8–1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4–3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution. Conclusion: Our findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS-based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.
KW - Arthroplasty, Replacement, Hip/adverse effects
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Multifactorial Inheritance
KW - Osteoarthritis, Hip/diagnostic imaging
KW - Osteoarthritis, Knee/diagnostic imaging
KW - Overweight/complications
KW - Risk Assessment
KW - Risk Factors
UR - http://www.scopus.com/inward/record.url?scp=85134625897&partnerID=8YFLogxK
U2 - 10.1002/art.42246
DO - 10.1002/art.42246
M3 - Article
C2 - 35644035
AN - SCOPUS:85134625897
SN - 2326-5191
VL - 74
SP - 1488
EP - 1496
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 9
ER -