ASSOCIATION OF HEALTHY LIFESTYLE, GENETIC SUSCEPTIBILITY AND INCIDENCE OF OSTEOARTHRITIS: A NATIONAL PROSPECTIVE COHORT STUDY

S. Chen, Y. Zhang, T. Fan, M. Zeng, J. LI, G. Ruan, P. Cao, Y. Zhang, X. Shi, X. Fang, H. Yang, Q. Yang, C. Ding, Z. ZhuSouthern Medical University, Clinical Research Centre, Zhujiang Hospital, Guangzhou, China Southern Medical University, Department of Epidemiology, School of Public Health, Guangzhou, China Southern Medical University, Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Guangzhou, China Guangzhou First People’s Hospital, Clinical Research Centre, Guangzhou, China University of Bristol, MRC Integrative Epidemiology Unit, Bristol, United Kingdom University of Tasmania, Menzies Institute for Medical Research, Hobart, Australia Southern Medical University, Department of Orthopaedics, Zhujiang Hospital, Guangzhou, China  Background Osteoarthritis (OA) is the commonest arthritis worldwide and affects approximately 7% of the global population. Previous studies reported that stick to a healthy lifestyle could reduce the risk of OA. However, whether and to what extent people with different genetic susceptibility of OA could benefit from a healthy lifestyle is still unknown. Objectives We aimed to detect the association between healthy lifestyle, genetic susceptibility and incident OA in the UK biobank study. Methods After excluding participants with missing data and performing multiple imputation, we included 317884 participants from UK biobank. Lifestyle factors included body mass index (BMI), diet, physical activity, sleep behavior and sedentary behavior. BMI lower than 30 kg/m2 was defined as healthy status. At least 4 of 7 healthy dietary components was defined as healthy diet. Medium level of physical activity (270-660 min/week) was classified as a healthy physical activity for OA. Healthy sleep behaviors were defined as sleep 7–8 h/day. Sedentary time less than 4 hours was regarded as low risk status. The healthy lifestyle score was constructed as the sum of five lifestyle factors, ranging from 0 to 5 and was subsequently categorized into three groups including unfavorable, intermediate and favorable (0–1, 2-3 and 4–5). Genetic susceptibility was calculated by using polygenic risk score (PRS) of OA. Specifically, individual single nucleotide polymorphism (SNP) was coded as 0, 1, and 2 according to the number of risk alleles. The coefficient of significant SNPs of OA reported in previous Genome Wide Association Studies (GWAS) were regarded as weight of genotype of each SNPs. Participants with OA were identified as having a diagnosis using ICD-9 and ICD-10 codes for total/ knee/ hip OA, or were identified as self-reported total/ knee/ hip OA at baseline. Covariates included age, sex, household income, education, deprivation index, glucosamine use and comorbidities. Cox regression analyses were performed to examine the association of healthy lifestyle, genetic susceptibility and incident OA. Results Comparing to unfavorable lifestyle, favorable lifestyle was significantly associated with a lower risk of total OA across low, intermediate and high genetic risk groups (HR, 0.64; 95%CI, 0.58-0.70; HR, 0.59; 95%CI, 0.56-0.63 and HR, 0.58; 95%CI, 0.53-0.64, respectively). Favorable lifestyle was also significantly associated with lower risk of knee OA across low, intermediate and high genetic risk groups (HR, 0.40; 95%CI, 0.33-0.48, HR, 0.47, 95%CI, 0.42-0.51 and HR, 0.45; 95%CI, 0.39-0.53, respectively). For hip OA, adherence to favorable lifestyle was also significantly associated with lower risk of OA incidence across low, intermediate and high genetic risk groups (HR, 0.75; 95%CI, 0.62-0.92, HR, 0.65, 95%CI, 0.58-0.72 and HR, 0.75; 95%CI, 0.65-0.88, respectively), compared to unfavorable lifestyle. No significant interaction was detected between lifestyle and PRS for total/ knee/ hip OA. Conclusion These data suggest that healthier lifestyle is consistently associated with lower risk of OA, regardless of genetic risks. Our findings highlight the importance of adherence to an overall healthy lifestyle in attenuating the risk of OA. References Hunter DJ, March L, Chew M. Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet 2020;396(10264):1711-12. doi: 10.1016/s0140-6736(20)32230-3 [published Online First: 2020/11/08] Gwinnutt JM, Wieczorek M, Balanescu A, et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis 2023;82(1):48-56. doi: 10.1136/annrheumdis-2021-222020 [published Online First: 2022/03/10] Figure 1. Association between healthy lifestyle score and total/ knee/ hip osteoarthritis stratified by different levels of genetic risk. Abbreviation: OA, osteoarthritis; HR, hazard ratio. P for interaction: interactions between low genetic risk and high genetic risk group. Image/graph: Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Lifestyles, Osteoarthritis, Genetics/Epigenetics DOI: 10.1136/annrheumdis-2023-eular.5985Citation: , volume 82, supplement 1, year 2023, page 96Session: Risk factors and their treatment in the progression of osteoarthritis (Oral Presentations)