{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T20:25:40Z","timestamp":1781555140317,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1157281"],"award-info":[{"award-number":["GNT1157281"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed 2\u2010sample MR using summary\u2010level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome\u2010wide association using the UK Biobank, and for site\u2010specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity\u2013osteoarthritis relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site\u2010specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (<jats:italic>P<\/jats:italic><jats:sub>nonlinear<\/jats:sub>\u00a0=\u00a00.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.24884","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:04:53Z","timestamp":1647867893000},"page":"885-892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Association Between Metabolically Different Adiposity Subtypes and Osteoarthritis: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-3454","authenticated-orcid":false,"given":"Anwar","family":"Mulugeta","sequence":"first","affiliation":[{"name":"University of South Australia and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, and Addis Ababa University  Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tesfahun C.","family":"Eshetie","sequence":"additional","affiliation":[{"name":"University of Washington  Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gizat M.","family":"Kassie","sequence":"additional","affiliation":[{"name":"University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Erku","sequence":"additional","affiliation":[{"name":"Griffith University, Nathan and Gold Coast  Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemayehu","family":"Mekonnen","sequence":"additional","affiliation":[{"name":"Deakin University  Geelong Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Lumsden","sequence":"additional","affiliation":[{"name":"University of South Australia and South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Hypp\u00f6nen","sequence":"additional","affiliation":[{"name":"University of South Australia and South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61729-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60802-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100587"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2011.05.015"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(19)30028-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2009.08.010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.136"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203772"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40928"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40812"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.12.015"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0079-y"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04124-9"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60681-3"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.08.10.24493"},{"key":"e_1_2_7_18_1","unstructured":"UK Biobank.First occurrence of health outcomes defined by 3\u2010character ICD10 code.2019. 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