{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:00:35Z","timestamp":1783792835273,"version":"3.55.0"},"reference-count":32,"publisher":"The Journal of Rheumatology","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"accepted":{"date-parts":[[2025,5,20]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate modifiable lifestyle-genetic susceptibility interactions with the risk of developing radiographic axial spondyloarthritis (r-axSpA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study included 382,035 individuals without r-axSpA at baseline in the UK Biobank. A combined lifestyle score consisting of 6 factors and a polygenic risk score (PRS) using r-axSpA\u2013associated genetic loci was constructed for each participant. Participants were further classified into 3 categories (unfavorable, intermediate, or favorable lifestyle) based on their score. Cox proportional hazards regression models were applied to evaluate the associations of lifestyle and PRS with risk of developing r-axSpA. Moreover, the association between lifestyle score and r-axSpA mediated by systemic inflammation was estimated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During a median follow-up period of 13.57 years, 694 patients with r-axSpA were diagnosed. With unfavorable lifestyle as the reference group, intermediate lifestyle (hazard ratio [HR] 0.67, 95% CI 0.57-0.80) and favorable lifestyle (HR 0.62, 95% CI 0.49-0.78) were associated with a decreased risk of developing r-axSpA. For the combined effect of lifestyle and PRS, participants with unfavorable lifestyle and high genetic risk had the highest risk of developing r-axSpA (HR 2.18, 95% CI 1.47-3.23) compared to those with favorable lifestyle and low genetic risk. However, no evidence of addictive and multiplicative interaction was observed. Further, mediation analyses revealed that the inverse association between healthy lifestyle score and the risk of developing r-axSpA was in part mediated by systemic inflammation, which ranged from 0.20% for neutrophil-to\u2013high-density lipoprotein cholesterol ratio to 10.29% for C-reactive protein.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study suggested that adherence to a favorable lifestyle significantly reduced the risk of developing r-axSpA by attenuating the systemic inflammatory response, which was independent of genetic susceptibility to r-axSpA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3899\/jrheum.2025-0042","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T08:20:24Z","timestamp":1749975624000},"page":"893-901","source":"Crossref","is-referenced-by-count":2,"title":["Modifiable Lifestyle Factors, Genetic Susceptibility, and Incident Radiographic Axial Spondyloarthritis"],"prefix":"10.3899","volume":"52","author":[{"given":"Ke","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8857-1550","authenticated-orcid":false,"given":"Zhixing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-7832","authenticated-orcid":false,"given":"Ding","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-0679","authenticated-orcid":false,"given":"James Cheng-Chung","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-9160","authenticated-orcid":false,"given":"Yingying","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"2025090105350877000_52.9.893.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60635-7"},{"key":"2025090105350877000_52.9.893.2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket387"},{"key":"2025090105350877000_52.9.893.3","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002302"},{"key":"2025090105350877000_52.9.893.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00625-y"},{"key":"2025090105350877000_52.9.893.5","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.210006"},{"key":"2025090105350877000_52.9.893.6","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa093"},{"key":"2025090105350877000_52.9.893.7","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00296-018-3927-2","article-title":"Alcohol and disease activity in axial spondyloarthritis: a cross-sectional study","volume":"38","author":"Zhao","year":"2018","journal-title":"Rheumatol Int"},{"key":"2025090105350877000_52.9.893.8","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/13548506.2019.1659984","article-title":"The effectiveness of aquatic physical therapy intervention on disease activity and function of ankylosing spondylitis patients: a meta-analysis","volume":"25","author":"Zhao","year":"2020","journal-title":"Psychol Health Med"},{"key":"2025090105350877000_52.9.893.9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.apmr.2017.07.015","article-title":"Effectiveness of exercise programs in ankylosing spondylitis: a meta-analysis of randomized controlled trials","volume":"99","author":"P\u00e9courneau","year":"2018","journal-title":"Arch Phys Med Rehabil"},{"key":"2025090105350877000_52.9.893.10","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2020-001225"},{"key":"2025090105350877000_52.9.893.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"2025090105350877000_52.9.893.12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-071707"},{"key":"2025090105350877000_52.9.893.13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/ije\/dyac238","article-title":"Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types","volume":"52","author":"Byrne","year":"2023","journal-title":"Int J Epidemiol"},{"key":"2025090105350877000_52.9.893.14","doi-asserted-by":"crossref","first-page":"435","DOI":"10.2337\/dc23-1503","article-title":"Modifiable lifestyle factors, genetic risk, and incident peripheral artery disease among individuals with type 2 diabetes: a prospective study","volume":"47","author":"Zhu","year":"2024","journal-title":"Diabetes Care"},{"key":"2025090105350877000_52.9.893.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2667"},{"key":"2025090105350877000_52.9.893.16","doi-asserted-by":"crossref","first-page":"e1004135","DOI":"10.1371\/journal.pmed.1004135","article-title":"Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: a cohort study","volume":"20","author":"Geng","year":"2023","journal-title":"PLoS Med"},{"key":"2025090105350877000_52.9.893.17","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00752-6"},{"key":"2025090105350877000_52.9.893.18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fendo.2019.00191","article-title":"The role of monocyte to high-density lipoprotein cholesterol ratio in prediction of carotid intima-media thickness in patients with type 2 diabetes","volume":"10","author":"Chen","year":"2019","journal-title":"Front Endocrinol"},{"key":"2025090105350877000_52.9.893.19","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1093\/rheumatology\/kead345","article-title":"Presence of periodontal disease and the incidence of inflammatory arthritides in the general population: data from the UK Biobank","volume":"63","author":"Yun","year":"2024","journal-title":"Rheumatology"},{"key":"2025090105350877000_52.9.893.20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13075-024-03266-0","article-title":"The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study","volume":"26","author":"Fei","year":"2024","journal-title":"Arthritis Res Ther"},{"key":"2025090105350877000_52.9.893.21","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001378"},{"key":"2025090105350877000_52.9.893.22","doi-asserted-by":"crossref","first-page":"e2350934","DOI":"10.1001\/jamanetworkopen.2023.50934","article-title":"Obesity, twin pregnancy, and the role of assisted reproductive technology","volume":"7","author":"Bone","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2025090105350877000_52.9.893.23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.9879"},{"key":"2025090105350877000_52.9.893.24","doi-asserted-by":"publisher","DOI":"10.1007\/s11121-007-0070-9"},{"key":"2025090105350877000_52.9.893.25","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-002170"},{"key":"2025090105350877000_52.9.893.26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s42358-023-00315-1","article-title":"Prevalence of sleep disturbance in patients with ankylosing spondylitis: a systematic review and meta-analysis","volume":"63","author":"Salari","year":"2023","journal-title":"Adv Rheumatol"},{"key":"2025090105350877000_52.9.893.27","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-021-05679-7"},{"key":"2025090105350877000_52.9.893.28","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.semarthrit.2021.04.004","article-title":"Efficacy of home-based physical activity interventions in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis","volume":"51","author":"Sieczkowska","year":"2021","journal-title":"Semin Arthritis Rheum"},{"key":"2025090105350877000_52.9.893.29","doi-asserted-by":"crossref","first-page":"887326","DOI":"10.3389\/fimmu.2022.887326","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":"2025090105350877000_52.9.893.30","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219446"},{"key":"2025090105350877000_52.9.893.31","doi-asserted-by":"crossref","first-page":"e23964","DOI":"10.1002\/jcla.23964","article-title":"Systemic immune-inflammation index is associated with disease activity in patients with ankylosing spondylitis","volume":"35","author":"Wu","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"2025090105350877000_52.9.893.32","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz241"}],"container-title":["The Journal of Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.3899\/jrheum.2025-0042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T12:35:25Z","timestamp":1756730125000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jrheum.org\/lookup\/doi\/10.3899\/jrheum.2025-0042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,1]]},"published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.3899\/jrheum.2025-0042"],"URL":"https:\/\/doi.org\/10.3899\/jrheum.2025-0042","relation":{},"ISSN":["0315-162X","1499-2752"],"issn-type":[{"value":"0315-162X","type":"print"},{"value":"1499-2752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}