{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T10:46:11Z","timestamp":1767091571584,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203918\/Z\/16\/Z","211030\/Z\/18\/Z"],"award-info":[{"award-number":["203918\/Z\/16\/Z","211030\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"publisher","award":["MC\u2010UU\u201000011\u20105"],"award-info":[{"award-number":["MC\u2010UU\u201000011\u20105"]}],"id":[{"id":"10.13039\/501100000883","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":[[2023,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Observational studies report mixed findings regarding the association between vitamin D and juvenile idiopathic arthritis (JIA) incidence or activity; however, such studies are susceptible to considerable bias. Because low vitamin D levels are common within the general population and easily corrected, there is potential public health benefit in identifying a causal association between vitamin D insufficiency and JIA incidence. To limit bias due to confounding and reverse causation, we examined the causal effect of the major circulating form of vitamin D, 25\u2010hydroxy vitamin D (25\u2010[OH]D), on JIA incidence using Mendelian randomization (MR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this 2\u2010sample MR analysis, we used summary level data from the largest and most recent genome\u2010wide association study of 25\u2010(OH)D levels (sample size 443,734), alongside summary data from 2 JIA genetic studies (sample sizes 15,872 and 12,501), all from European populations. To test and account for potential bias due to pleiotropy, we employed multiple MR methods and sensitivity analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found no evidence of a causal relationship between genetically predicted 25\u2010(OH)D levels and JIA incidence (odds ratio 1.00 [95% confidence interval (95% CI) 0.76, 1.33] per SD increase in standardized natural\u2010log transformed 25\u2010[OH]D levels). This estimate was consistent across all methods tested. Additionally, there was no evidence that genetically predicted JIA causally influences 25\u2010(OH)D levels (\u22120.002 SD change in standardized natural\u2010log transformed 25\u2010[OH]D levels per doubling odds in genetically predicted JIA [95% CI \u22120.006, 0.002]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Given the lack of a causal relationship between 25\u2010(OH)D levels and JIA, population level vitamin D supplementation is unlikely to reduce JIA incidence.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.24815","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T09:02:07Z","timestamp":1636362127000},"page":"674-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Vitamin D Levels and Risk of Juvenile Idiopathic Arthritis: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7385-6307","authenticated-orcid":false,"given":"Sarah L. 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