{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:05:33Z","timestamp":1784099133517,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2026J001374"],"award-info":[{"award-number":["2026J001374"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Sports Act. Living"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Physical activities have consistently been associated with rheumatoid arthritis risk. However, there is limited evidence regarding their associations according to different genetic susceptibility to the disease, and it remains poorly understood whether systemic inflammation and lipids may mediate this association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the association between physical activity and risk of rheumatoid arthritis, a multivariable Cox regression was performed using data from 351,857 participants in UK Biobank cohort. Additionally, we assessed the interaction of physical activity with polygenic risk score (PRS) for rheumatoid arthritis. We further estimated the percentage of total association between physical activity and rheumatoid arthritis that is mediated by C-reactive protein (CRP) and lipids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A lower risk of rheumatoid arthritis was associated with the moderate and high level of physical activity (HR\u2009=\u20090.77, 95%CI\u2009=\u20090.70\u20130.84 and HR\u2009=\u20090.82, 95%CI\u2009=\u20090.75\u20130.89, respectively), and this association was stronger with five year after baseline. Separated by intensity of physical activity, only vigorous activity was associated with reduced risk of rheumatoid arthritis. A significant interaction was observed between physical activity and PRS for rheumatoid arthritis, indicating stronger association in those with low or medium genetic predisposition to rheumatoid arthritis. Furthermore, BMI and CRP was found to mediate 33.73% and 32.89% of the associations between physical activity and rheumatoid arthritis, while high-density lipoprotein (HDL) mediated 15.61% of the association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We observed an inverse association between physical activity and risk of rheumatoid arthritis in UK biobank, which was stronger in those with low or medium PRS. BMI, CRP and HDL may be key intermediates in the association, suggesting them as potential monitoring biomarker for physical activity intervention to prevent rheumatoid arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fspor.2026.1851796","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:10:24Z","timestamp":1784095824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Physical activity, genetic predisposition and the risk of rheumatoid arthritis: a prospective cohort study"],"prefix":"10.3389","volume":"8","author":[{"given":"Yuanming","family":"Zhong","sequence":"first","affiliation":[{"name":"School of Physical Education and Sport Science, Fujian Normal University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, The Affiliated Huaian No.1 People\u2019s Hospital of Nanjing Medical University","place":["Huaian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Dalian Medical University, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport Science, Fujian Normal University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haomin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport Science, Fujian Normal University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41584-021-00652-9","article-title":"Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases","volume":"17","author":"Szekanecz","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.5114\/aoms\/162629","article-title":"Increasing global burden of rheumatoid arthritis: an epidemiological analysis from 1990 to 2019","volume":"19","author":"Zou","year":"2023","journal-title":"Arch Med Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13075-015-0560-2","article-title":"Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study","volume":"17","author":"Di Giuseppe","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1002\/art.40899","article-title":"Long-term physical activity and subsequent risk for rheumatoid arthritis among women: a prospective cohort study","volume":"71","author":"Liu","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1186\/s12916-024-03615-5","article-title":"Sleep patterns, physical activity, genetic susceptibility, and incident rheumatoid arthritis: a prospective cohort study","volume":"22","author":"Ni","year":"2024","journal-title":"BMC Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2147\/OARRR.S203511","article-title":"Physical activity and sedentary behavior in women with rheumatoid arthritis: a comparison of patients with low and high disease activity and healthy controls","volume":"11","author":"Summers","year":"2019","journal-title":"Open Access Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/ije\/dyab052","article-title":"Physical activity and the risk of rheumatoid arthritis: evidence from meta-analysis and Mendelian randomization","volume":"50","author":"Sun","year":"2021","journal-title":"Int J Epidemiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2018.09.002","article-title":"Myokines, physical activity, insulin resistance and autoimmune diseases","volume":"203","author":"D\u00edaz","year":"2018","journal-title":"Immunol Lett"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3899\/jrheum.220788","article-title":"How could physical activity reduce inflammation and inflammatory gene expression in rheumatoid arthritis?","volume":"49","author":"Dessein","year":"2022","journal-title":"J Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12967-023-03939-5","article-title":"Robust SNP-based prediction of rheumatoid arthritis through machine-learning-optimized polygenic risk score","volume":"21","author":"Lim","year":"2023","journal-title":"J Transl Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e003560","DOI":"10.1136\/rmdopen-2023-003560","article-title":"Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK biobank","volume":"9","author":"Fang","year":"2023","journal-title":"RMD open"},{"key":"B12","doi-asserted-by":"publisher","first-page":"901223","DOI":"10.3389\/fimmu.2022.901223","article-title":"Systematic evaluation of rheumatoid arthritis risk by integrating lifestyle factors and genetic risk scores","volume":"13","author":"Yu","year":"2022","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"921085","DOI":"10.3389\/fimmu.2022.921085","article-title":"Effect of exercise training on body composition and inflammatory cytokine levels in overweight and obese individuals: a systematic review and network meta-analysis","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1001\/jama.2010.1843","article-title":"Maintaining a high physical activity level over 20 years and weight gain","volume":"304","author":"Hankinson","year":"2010","journal-title":"JAMA"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.3390\/nu12061899","article-title":"The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: a review","volume":"12","author":"Gonzalez-Gil","year":"2020","journal-title":"Nutrients"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e70080","DOI":"10.1002\/iid3.70080","article-title":"Obesity and chronic inflammation: implications for rheumatoid arthritis, spondyloarthritis, and ulcerative colitis","volume":"13","author":"Corrado","year":"2025","journal-title":"Immun Inflamm Dis"},{"key":"B17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.semarthrit.2008.01.015","article-title":"Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment","volume":"38","author":"Steiner","year":"2009","journal-title":"Semin Arthritis Rheum"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1190607","DOI":"10.3389\/fimmu.2023.1190607","article-title":"Lipid metabolism and rheumatoid arthritis","volume":"14","author":"Lei","year":"2023","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"B20","year":""},{"key":"B21","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/S1047-2797(99)00022-8","article-title":"Intra-individual variation and estimates of usual physical activity","volume":"9","author":"Levin","year":"1999","journal-title":"Ann Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0307270","DOI":"10.1371\/journal.pone.0307270","article-title":"A systematic evaluation of the performance and properties of the UK biobank polygenic risk score (PRS) release","volume":"19","author":"Thompson","year":"2024","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1017\/jns.2017.66","article-title":"Dietary assessment in UK biobank: an evaluation of the performance of the touchscreen dietary questionnaire","volume":"7","author":"Bradbury","year":"2018","journal-title":"J Nutr Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/ije\/dym276","article-title":"The UK biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine","volume":"37","author":"Elliott","year":"2008","journal-title":"Int J Epidemiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"i2","DOI":"10.1093\/ije\/dyn019","article-title":"The UK biobank sample handling and storage validation studies","volume":"37","author":"Peakman","year":"2008","journal-title":"Int J Epidemiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1002\/sim.3473","article-title":"Comments on \u2018choice of time scale and its effect on significance of predictors in longitudinal studies\u2019 by Michael J. Pencina, Martin G. Larson and Ralph B. D'Agostino, statistics in medicine 2007; 26:1343-1359","volume":"28","author":"Gail","year":"2009","journal-title":"Stat Med"},{"key":"B27","author":"Discacciati","year":""},{"key":"B28","article-title":"Causal relationships between total physical activity and ankylosing spondylitis: a Mendelian randomization study","volume":"13","author":"Hu","year":"2022","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"872126","DOI":"10.3389\/fimmu.2022.872126","article-title":"Physical activity and risk of multiple sclerosis: a Mendelian randomization study","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3390\/antiox11020350","article-title":"Effects of exercise training on the autonomic nervous system with a focus on anti-inflammatory and antioxidants effects","volume":"11","author":"Daniela","year":"2022","journal-title":"Antioxidants"},{"key":"B31","doi-asserted-by":"publisher","first-page":"102974","DOI":"10.1016\/j.arr.2025.102974","article-title":"Exercise-induced inflammatory and metabolic adaptations in ageing: a meta-analytic compendium","volume":"114","author":"Sheldon","year":"2026","journal-title":"Ageing Res Rev"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.berh.2017.08.003","article-title":"Genetic and environmental risk factors for rheumatoid arthritis","volume":"31","author":"Deane","year":"2017","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1750640","DOI":"10.3389\/fmed.2025.1750640","article-title":"Association of body mass index with the risk of rheumatoid arthritis: a systematic review and meta-analysis","volume":"12","author":"Cao","year":"2026","journal-title":"Front Med (Lausanne)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.aller.2013.11.003","article-title":"Inflammatory markers in patients with rheumatoid arthritis","volume":"43","author":"Shrivastava","year":"2015","journal-title":"Allergol Immunopathol (Madr)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.jjcc.2017.08.008","article-title":"Chronic kidney disease, inflammation, and cardiovascular disease risk in rheumatoid arthritis","volume":"71","author":"Kochi","year":"2018","journal-title":"J Cardiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.2337\/db06-1656","article-title":"Visceral fat adipokine secretion is associated with systemic inflammation in obese humans","volume":"56","author":"Fontana","year":"2007","journal-title":"Diabetes"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e148552","DOI":"10.1172\/JCI148552","article-title":"Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies","volume":"132","author":"Robinson","year":"2022","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.ijbiomac.2021.12.009","article-title":"High-density lipoproteins and immune response: a review","volume":"195","author":"Grao-Cruces","year":"2022","journal-title":"Int J Biol Macromol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4676","DOI":"10.4049\/jimmunol.1402870","article-title":"High-density lipoprotein attenuates Th1 and Th17 autoimmune responses by modulating dendritic cell maturation and function","volume":"194","author":"Tiniakou","year":"2015","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/acr.25662","article-title":"Accuracy of diagnostic codes and algorithms used to identify rheumatoid arthritis and juvenile idiopathic arthritis in administrative claims and electronic health records","volume":"78","author":"Saka-Herr\u00e1n","year":"2026","journal-title":"Arthritis Care Res"}],"container-title":["Frontiers in Sports and Active Living"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fspor.2026.1851796\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:10:26Z","timestamp":1784095826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fspor.2026.1851796\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":40,"alternative-id":["10.3389\/fspor.2026.1851796"],"URL":"https:\/\/doi.org\/10.3389\/fspor.2026.1851796","relation":{},"ISSN":["2624-9367"],"issn-type":[{"value":"2624-9367","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1851796"}}