{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:02:03Z","timestamp":1776902523022,"version":"3.51.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Observational studies suggest that vitamin D supplementation may be effective in preventing myasthenia gravis (MG). However, the causal relationship between circulating vitamin D levels and MG remains unclear. This study aimed to examine the genetic causality of circulating vitamin D and MG using data from large population-based genome-wide association studies (GWAS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SNPs (single nucleotide polymorphisms) strongly associated with exposure were selected. Two-sample Mendelian Randomization (MR) was performed with inverse variance weighting (IVW), MR-Egger (Mendelian randomization-Egger), weight median and MR-PRESSO (Mendelian randomization pleiotropy residual sum and outlier) methods. Heterogeneity was tested via IVW and MR-Egger. Pleiotropy was tested using MR-Egger intercept test and MR-PRESSO method. MR-PRESSO was also used to detect outliers. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In IVW, circulating vitamin D levels had no causal effect on MG [OR\u2009=\u20090.91 (0.67\u20131.22), <jats:italic>p<\/jats:italic>\u2009=\u20090.532] and MG had no causal effect on circulating vitamin D [OR\u2009=\u20091.01 (099\u20131.02), <jats:italic>p<\/jats:italic>\u2009=\u20090.663]. No heterogeneity or pleiotropy was observed (<jats:italic>p<\/jats:italic>\u2009&amp;gt;\u20090.05). Other MR methods also agreed with IVW results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides the causal relationship between genetically predicted circulating vitamin D levels and MG and provides new insights into the genetics of MG.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2023.1171830","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T06:42:48Z","timestamp":1689748968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Causal effect of vitamin D on myasthenia gravis: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"10","author":[{"given":"Yidan","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaiying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangda","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiashi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenwei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1212\/WNL.0b013e3181ad53c2","article-title":"Seropositive myasthenia gravis: a nationwide epidemiologic study","volume":"73","author":"Heldal","year":"2009","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1471-2377-10-46","article-title":"A systematic review of population based epidemiological studies in myasthenia gravis","volume":"10","author":"Carr","year":"2010","journal-title":"BMC Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.12688\/f1000research.8206.1","article-title":"Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms","volume":"5","author":"Phillips","year":"2016","journal-title":"F1000Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41422-020-0324-7","article-title":"Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases","volume":"30","author":"Ohkura","year":"2020","journal-title":"Cell Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/j.1749-6632.2012.06840.x","article-title":"Functional defect in regulatory T cells in myasthenia gravis","volume":"1274","author":"Thiruppathi","year":"2012","journal-title":"Ann N Y Acad Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jneuroim.2015.03.008","article-title":"Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity","volume":"281","author":"Alahgholi-Hajibehzad","year":"2015","journal-title":"J Neuroimmunol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1111\/php.13432","article-title":"Low vitamin D serum levels in a cohort of myasthenia gravis patients in Argentina","volume":"97","author":"Justo","year":"2021","journal-title":"Photochem Photobiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jocn.2018.01.047","article-title":"Low serum vitamin D levels in patients with myasthenia gravis","volume":"50","author":"Kang","year":"2018","journal-title":"J Clin Neurosci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1111\/j.1468-1331.2012.03773.x","article-title":"Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study","volume":"19","author":"Askmark","year":"2012","journal-title":"Eur J Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s13760-015-0512-2","article-title":"Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece","volume":"116","author":"Chroni","year":"2016","journal-title":"Acta Neurol Belg"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1007\/s00198-017-4041-0","article-title":"Association between bone mineral density, muscle strength, and vitamin D status in patients with myasthenia gravis: a cross-sectional study","volume":"28","author":"Guan","year":"2017","journal-title":"Osteoporos Int"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"012032","DOI":"10.1088\/1742-6596\/1246\/1\/012032","article-title":"Effect of vitamin D3 supplementation towards vitamin D serum levels and myasthenia gravis composite score (MGCS)","volume":"1246","author":"Okparasta","year":"2019","journal-title":"J Phys Conf Ser"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1093\/ije\/dyh023","article-title":"Commentary: Mendelian randomization, 18 years on","volume":"33","author":"Katan","year":"2004","journal-title":"Int J Epidemiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1038\/s41467-020-15421-7","article-title":"Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration","volume":"11","author":"Revez","year":"2020","journal-title":"Nat Commun"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/s41467-017-02662-2","article-title":"Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels","volume":"9","author":"Jiang","year":"2018","journal-title":"Nat Commun"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e2108672119","DOI":"10.1073\/pnas.2108672119","article-title":"Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study","volume":"119","author":"Chia","year":"2022","journal-title":"Proc Natl Acad Sci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics J Integr Biol"},{"key":"ref20","first-page":"1","article-title":"Enrichplot: visualization of functional enrichment result","volume":"1","author":"Yu","year":"2019","journal-title":"R Package Version"},{"key":"ref21","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"Wickham","year":"2016"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"731","DOI":"10.21105\/joss.00731","article-title":"Qqman: an R package for visualizing GWAS results using Q-Q and Manhattan plots","volume":"3","author":"Turner","year":"2018","journal-title":"J Open Source Softw"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int J Epidemiol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e0120758","DOI":"10.1371\/journal.pone.0120758","article-title":"A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians","volume":"10","author":"Shim","year":"2015","journal-title":"PLoS One"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4161\/derm.24494","article-title":"Sunlight and vitamin D: A global perspective for health","volume":"5","author":"Wacker","year":"2013","journal-title":"Dermatoendocrinol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol Rev"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3109\/00365513.2012.681892","article-title":"Metabolism and biomarkers of vitamin D","volume":"243","author":"Jones","year":"2012","journal-title":"Scand J Clin Lab Investig Suppl"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3389\/fimmu.2016.00697","article-title":"Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential","volume":"7","author":"Dankers","year":"2016","journal-title":"Front Immunol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"752","DOI":"10.2174\/1871527321666220707111344","article-title":"Myasthenia gravis and vitamin D serum levels: a systematic review and meta-analysis","volume":"22","author":"Bonaccorso","year":"2022","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1056\/NEJM198205133061903","article-title":"Calcium homeostasis in immobilization: an example of resorptive hypercalciuria","volume":"306","author":"Stewart","year":"1982","journal-title":"N Engl J Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/qjmed\/hct208","article-title":"Plasma exchange induces vitamin D deficiency","volume":"107","author":"Hiemstra","year":"2014","journal-title":"QJM"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"51","DOI":"10.12659\/ajcr.894849","article-title":"Remission of severe myasthenia gravis after massive-dose vitamin D treatment","volume":"17","author":"Cadegiani","year":"2016","journal-title":"Am J Case Rep"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"171","DOI":"10.36502\/2020\/ASJBCCR.6208","article-title":"Myasthenia gravis in pregnancy treated with daily massive vitamin D dose","volume":"3","author":"Lff","year":"2020","journal-title":"Asploro J Biomed Clin Case Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3389\/fimmu.2020.00212","article-title":"Autoantibody specificities in myasthenia gravis; implications for improved diagnostics and therapeutics","volume":"11","author":"Lazaridis","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1171830\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T06:42:56Z","timestamp":1689748976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1171830\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":39,"alternative-id":["10.3389\/fnut.2023.1171830"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2023.1171830","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,19]]},"article-number":"1171830"}}