Associations of healthy lifestyle and genetic susceptibility with risks of osteoarthritis: A prospective cohort study

Shibo Chen; Yujie Zhang; Tianxiang Fan; Muhui Zeng; Qian Yang; Hao Yang; Xiaofeng Fang; Xingzhong Jin; Peihua Cao; Zhiqiang Wang; Yan Zhang; David J Hunter; Yuan Zhou; GO consortium; arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, Regeneron Genetics Center; Changhai Ding; Zhaohua Zhu

doi:10.1093/rheumatology/keaf327

Associations of healthy lifestyle and genetic susceptibility with risks of osteoarthritis: A prospective cohort study

Rheumatology (Oxford). 2025 Jun 20:keaf327. doi: 10.1093/rheumatology/keaf327. Online ahead of print.

Authors

Shibo Chen^{1

2}, Yujie Zhang³, Tianxiang Fan^{1

4}, Muhui Zeng^{1

5}, Qian Yang^{6

7}, Hao Yang¹, Xiaofeng Fang¹, Xingzhong Jin^{8

9}, Peihua Cao¹, Zhiqiang Wang¹, Yan Zhang¹, David J Hunter^{1

10}, Yuan Zhou¹¹; GO consortium; arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, Regeneron Genetics Center; Changhai Ding^{1

12

13}, Zhaohua Zhu^{1

14}

Collaborators Collaborators

GO consortium:
Cindy G Boer, Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefánsdóttir, Yanfei Zhang, Rodrigo Coutinho de Almeida, Tian T Wu, Jie Zheng, April Hartley, Maris Teder-Laving, Anne Heidi Skogholt, Chikashi Terao, Eleni Zengini, George Alexiadis, Andrei Barysenka, Gyda Bjornsdottir, Maiken E Gabrielsen, Arthur Gilly, Thorvaldur Ingvarsson, Marianne B Johnsen, Helgi Jonsson, Margreet Kloppenburg, Almut Luetge, Sigrun H Lund, Reedik Mägi, Massimo Mangino, Rob R G H H Nelissen, Manu Shivakumar, Julia Steinberg, Hiroshi Takuwa, Laurent F Thomas, Margo Tuerlings
arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, Regeneron Genetics Center:
George C Babis, Jason Pui Yin Cheung, Jae Hee Kang, Peter Kraft, Steven A Lietman, Dino Samartzis, P Eline Slagboom, Kari Stefansson, Unnur Thorsteinsdottir, Jonathan H Tobias, André G Uitterlinden, Bendik Winsvold, John-Anker Zwart, George Davey Smith, Pak Chung Sham, Gudmar Thorleifsson, Tom R Gaunt, Andrew P Morris, Ana M Valdes, Aspasia Tsezou, Kathryn S E Cheah, Shiro Ikegawa, Kristian Hveem, Tõnu Esko, J Mark Wilkinson, Ingrid Meulenbelt, Ming Ta Michael Lee, Joyce B J van Meurs, Unnur Styrkársdóttir, Eleftheria Zeggini

Affiliations

¹ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
² Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
³ Fujian Provincial Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
⁴ Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China.
⁵ Department of Orthopedics, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, China.
⁶ MRC Integrative Epidemiology Unit at University of Bristol, Bristol, United Kingdom.
⁷ Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom.
⁸ Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia.
⁹ Sydney Musculoskeletal Health, Kolling Institute, The University of Sydney, Sydney, Australia.
¹⁰ Department of Rheumatology, Royal North Shore Hospital and Sydney Musculoskeletal Health, Kolling Institute, University of Sydney, Sydney, 2065, Australia.
¹¹ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
¹² Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
¹³ Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.
¹⁴ Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

PMID: 40578805
DOI: 10.1093/rheumatology/keaf327

Abstract

Objectives: To detect the associations of a healthy lifestyle and genetic susceptibility with incident osteoarthritis (OA) in the UK biobank study.

Methods: We included 314 729 participants from UK biobank. Five modifiable lifestyle factors including weight management, diet, physical activity, sleep behavior and sedentary behavior were included to generate an overall lifestyle score. Genetic susceptibility was calculated by using polygenic risk score (PRS) of OA. Participants diagnosed with OA were identified by using ICD-9 and ICD-10. Covariates included age, sex, education, Townsend deprivation index, glucosamine use, analgesics use and comorbidities. Cox regression analyses were performed to examine the associations of genetic susceptibility and healthy lifestyle with incident OA.

Results: Adopting a more favorable lifestyle can be beneficial in significantly reducing the risk of incident total, knee and hip OA (all p < 0.01). PRS was significantly associated with greater risks of total, knee and hip OA. Compared with unfavorable lifestyle, favorable lifestyle was significantly associated with a lower risk of total OA across low (HR, 0.64; 95%CI, 0.58-0.70), intermediate (HR, 0.59; 95%CI, 0.56-0.63) and high genetic risk groups (HR, 0.58; 95%CI, 0.53-0.64). Similar results were observed on knee OA and hip OA. No significant interactions were detected between lifestyle and PRS for total, knee or hip OA.

Conclusion: These data suggest that a healthier lifestyle is consistently associated with a 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.

Keywords: Osteoarthritis; lifestyle; polygenic risk.

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