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Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.<\/jats:p>","DOI":"10.1073\/pnas.2302259121","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T15:05:17Z","timestamp":1707750317000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Evidence supports a causal association between allele-specific vitamin D receptor binding and multiple sclerosis among Europeans"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-523X","authenticated-orcid":false,"given":"Cameron","family":"Adams","sequence":"first","affiliation":[{"name":"Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-5762","authenticated-orcid":false,"given":"Ali","family":"Manouchehrinia","sequence":"additional","affiliation":[{"name":"Division of Neuro, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden"},{"name":"The Karolinska Neuroimmunology &amp; 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