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

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, Changhai Ding^{1

12

13}, Zhaohua Zhu^{1

10

14

15}; GO Consortium

Collaborators, Affiliations

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, 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, 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, University of Bristol, Bristol, UK.
⁷ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
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, 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, China.
¹³ Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
¹⁴ Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
¹⁵ The George Institute for Global Health, UNSW, Sydney, NSW, Australia.

PMID: 40578805
DOI: 10.1093/rheumatology/keaf327

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

Shibo Chen et al. Rheumatology (Oxford). 2025.

. 2025 Nov 1;64(11):5673-5680.

doi: 10.1093/rheumatology/keaf327.

Authors

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, 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, 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, University of Bristol, Bristol, UK.
⁷ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
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, 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, China.
¹³ Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
¹⁴ Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
¹⁵ The George Institute for Global Health, UNSW, Sydney, NSW, Australia.

PMID: 40578805
DOI: 10.1093/rheumatology/keaf327

Abstract

Objectives: To detect the associations of a healthy lifestyle and genetic susceptibility with incident 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 behaviour and sedentary behaviour 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 the International Classification of Diseases (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 favourable 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 unfavourable lifestyle, favourable lifestyle was significantly associated with a lower risk of total OA across low [hazard ratio (HR) 0.64; 95% CI 0.58-0.70], intermediate (HR 0.59; 95% CI 0.56-0.63) and high (HR 0.58; 95% CI 0.53-0.64) genetic risk groups. 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: lifestyle; osteoarthritis; polygenic risk.

© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical