{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:35:25Z","timestamp":1786523725484,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objective: Genetic factors contribute to physical activity (PA) and sedentary behavior (SB), two complex behavioral traits. They may be associated with musculoskeletal and inflammatory diseases. However, the relationships of domain-specific PA and SB traits with osteoporosis (OS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) remain unclear. A two-sample Mendelian randomization (MR) analysis assessed potential bidirectional associations between these behavioral traits and the three diseases. Methods: GWAS summary statistics were used to examine five domain-specific PA traits, three SB traits, and OS, RA, and PsA. Primary causal estimates were obtained using the inverse-variance weighted (IVW) method. Complementary analyses used MR-Egger regression, the weighted median method, and the weighted mode method. Sensitivity analyses were performed using Cochran\u2019s Q test, the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Multiple testing was addressed using false discovery rate (FDR) correction. Results: In the forward MR analyses, genetically predicted liability to Light DIY was associated with lower odds of PsA after FDR correction (OR = 0.006, 95% CI = 0.0002\u20130.236, FDR-adjusted p = 0.018). Genetically predicted longer television viewing was linked to increased odds of PsA (OR = 2.205, 95% CI = 1.089\u20134.463, FDR-adjusted p = 0.028) and RA (OR = 1.006, 95% CI = 1.002\u20131.010, FDR-adjusted p = 0.004). Walking for pleasure showed a nominal inverse association with PsA, and computer use showed a nominal inverse association with RA. Neither association remained significant after FDR correction. No evidence of associations with the broad self-reported OS diagnosis was observed. Reverse MR analyses showed lower odds of Walking for pleasure (OR = 0.662, 95% CI = 0.484\u20130.906, FDR-adjusted p = 0.013) and Other exercises (OR = 0.651, 95% CI = 0.490\u20130.864, FDR-adjusted p = 0.006) for genetic liability to RA. RA liability was also associated with longer television viewing time (\u03b2 = 0.708, 95% CI = 0.251\u20131.165, FDR-adjusted p = 0.006). No reverse associations were observed for PsA. Conclusions: This bidirectional MR study identified several potential genetically predicted associations of domain-specific PA and SB traits with PsA and RA. The findings for television viewing and RA may suggest a potential bidirectional association. However, the results should be considered hypothesis-generating. These findings require independent replication and further validation before causal or clinical conclusions can be drawn.<\/jats:p>","DOI":"10.3390\/genes17080939","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Evidence for Causal Effects of Domain-Specific Physical Activity and Sedentary Behavior on Osteoporosis and Inflammatory Arthritis: A Bidirectional Mendelian Randomization Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Tianyu","family":"Sun","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, 1268 Middle Guangzhou Avenue, Guangzhou 510500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, 1268 Middle Guangzhou Avenue, Guangzhou 510500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-3370","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, 1268 Middle Guangzhou Avenue, Guangzhou 510500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1097\/CM9.0000000000002678","article-title":"Osteoimmunology research in rheumatoid arthritis: From single-cell omics approach","volume":"136","author":"Hu","year":"2023","journal-title":"Chin. 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