{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:09:13Z","timestamp":1790665753453,"version":"4.1.0"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000381","name":"Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["88"],"award-info":[{"award-number":["88"]}],"id":[{"id":"10.13039\/501100000381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Low serum 25(OH)D<jats:sub>3<\/jats:sub>(vD) is an environmental risk factor for multiple sclerosis (MS). Lower vD levels during early disease may be associated with long-term disability. Determinants of serum vD levels in healthy individuals include supplementation behaviour and genetic factors. These determinants have been less well studied in people with MS (pwMS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D<jats:sub>3<\/jats:sub>and genotyped six vD-associated SNPs (rs12785878, rs10741657, rs17216707, rs10745742, rs8018720, rs2282679) in a cohort of pwMS (<jats:italic>n<\/jats:italic>\u2009=\u2009315) with age and geographically matched controls (<jats:italic>n<\/jats:italic>\u2009=\u2009232). We then assessed predictors of serum vD concentration in this cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GRS was strongly associated with vD status in the Biobank cohort (<jats:italic>p<\/jats:italic>\u2009&lt;\u20092\u2009\u00d7\u200910<jats:sup>\u201316<\/jats:sup>). vD supplementation, having MS, lower BMI, increased age and supplementation dose were associated with higher vD levels (false discovery rate,\u00a0FDR\u2009&lt;\u20095%). In multivariable models adjusting for supplementation, BMI, age, sex, and MS status, the GRS was strongly associated with vD level (<jats:italic>p<\/jats:italic>\u2009=\u20090.004), but not in those who supplemented (<jats:italic>p<\/jats:italic>\u2009=\u20090.47).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00415-022-11466-4","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T10:08:47Z","timestamp":1667642927000},"page":"1030-1035","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vitamin D genetic risk scores in multiple sclerosis"],"prefix":"10.1007","volume":"270","author":[{"given":"Ashvin","family":"Kuri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Vickaryous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amine","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Meir","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-585X","authenticated-orcid":false,"given":"Ruth","family":"Dobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"issue":"1","key":"11466_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1212\/01.WNL.0000101723.79681.38","volume":"62","author":"KL Munger","year":"2004","unstructured":"Munger KL, Zhang SM, O\u2019Reilly E, Hern\u00e1n MA, Olek MJ, Willett WC, Ascherio A (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60\u201365","journal-title":"Neurology"},{"issue":"2","key":"11466_CR2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000662","volume":"7","author":"BM Jacobs","year":"2020","unstructured":"Jacobs BM, Noyce AJ, Giovannoni G, Dobson R (2020) BMI and low vitamin D are causal factors for multiple sclerosis: a mendelian randomization study. Neurol Neuroimmunol Neuroinflamm 7(2):e662","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"3","key":"11466_CR3","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1001\/jamaneurol.2013.5993","volume":"71","author":"A Ascherio","year":"2014","unstructured":"Ascherio A, Munger KL, White R, K\u00f6chert K, Simon KC, Polman CH, Freedman MS, Hartung HP, Miller DH, Montalb\u00e1n X, Edan G, Barkhof F, Pleimes D, Rad\u00fc EW, Sandbrink R, Kappos L, Pohl C (2014) Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 71(3):306\u2013314","journal-title":"JAMA Neurol"},{"issue":"2","key":"11466_CR4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ana.22043","volume":"68","author":"S Simpson Jr","year":"2010","unstructured":"Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van der Mei I (2010) Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 68(2):193\u2013203","journal-title":"Ann Neurol"},{"issue":"2","key":"11466_CR5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/ana.23591","volume":"72","author":"EM Mowry","year":"2012","unstructured":"Mowry EM, Waubant E, McCulloch CE, Okuda DT, Evangelista AA, Lincoln RR, Gourraud PA, Brenneman D, Owen MC, Qualley P, Bucci M, Hauser SL, Pelletier D (2012) Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 72(2):234\u2013240","journal-title":"Ann Neurol"},{"issue":"9736","key":"11466_CR6","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0140-6736(10)60588-0","volume":"376","author":"TJ Wang","year":"2010","unstructured":"Wang TJ et al (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376(9736):180\u2013188. https:\/\/doi.org\/10.1016\/S0140-6736(10)60588-0","journal-title":"Lancet"},{"issue":"1","key":"11466_CR7","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/s41467-017-02662-2","volume":"9","author":"X Jiang","year":"2018","unstructured":"Jiang X et al (2018) Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun 9(1):260","journal-title":"Nat Commun"},{"issue":"1","key":"11466_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s12031-018-1152-9","volume":"66","author":"L Agnello","year":"2018","unstructured":"Agnello L, Scazzone C, Lo Sasso B, Ragonese P, Milano S, Salemi G, Ciaccio M (2018) CYP27A1, CYP24A1, and RXR-\u03b1 polymorphisms, vitamin D, and multiple sclerosis: a pilot study. J Mol Neurosci 66(1):77\u201384","journal-title":"J Mol Neurosci"},{"issue":"3","key":"11466_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, Liu B, Matthews P, Ong G, Pell J, Silman A, Young A, Sprosen T, Peakman T, Collins R (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. 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Mult Scler 23(1):36\u201342","journal-title":"Mult Scler"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11466-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-022-11466-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11466-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T04:43:39Z","timestamp":1701319419000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-022-11466-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,5]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["11466"],"URL":"https:\/\/doi.org\/10.1007\/s00415-022-11466-4","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,5]]},"assertion":[{"value":"10 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors report no conflicts of interest with direct relevance to this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study had ethical permission via London Stanmore REC (18\/LO\/1455). UK Biobank has separate ethical approval; this work was performed under application 43,101 (REC approval 11\/NW\/0382).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard"}},{"value":"All participants gave informed consent on Biobank registration and are free to withdraw from the study at any point, at which point their data are censored and cannot be included in further analyses.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}