{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T05:04:59Z","timestamp":1766466299819,"version":"3.37.3"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Autonomous Region Key Research and Development Project","award":["2023B03003"],"award-info":[{"award-number":["2023B03003"]}]},{"name":"the Tian-Shan Talent Program","award":["2022TSYCLJ0066"],"award-info":[{"award-number":["2022TSYCLJ0066"]}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371258"],"award-info":[{"award-number":["82371258"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Central Guiding Local Science and Technology Development Special Fund Project","award":["ZYYD2022C17"],"award-info":[{"award-number":["ZYYD2022C17"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder, primarily characterized by motor impairments. Vitamin D has several regulatory functions in nerve cell survival and gene expression via its receptors. Although research has shown that vitamin D deficiency is prevalent among PD patients, the causal link to PD risk remains unclear. This study aims to investigate the causal relationship between vitamin D and PD using a bidirectional two-sample Mendelian randomization (MR) analysis method.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study applied a bidirectional two-sample MR analysis to explore the causal link between vitamin D and PD. We selected statistically significant single nucleotide polymorphisms (SNPs) related to 25-hydroxyvitamin D (25(OH)D) as instrumental variables (IVs), ensuring no association with known confounders. The analysis used GWAS data from over 1.2 million Europeans across four major published datasets, elucidating the genetic correlation between vitamin D levels and PD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We identified 148 instrumental SNPs associated with 25(OH)D. After adjustment for confounding-related SNPs, 131 SNPs remained in the analysis. Data from three PD cohorts revealed no significant correlation between 25(OH)D levels and PD risk using the IVW method (<jats:italic>P<\/jats:italic><jats:sub>cohort1<\/jats:sub> = 0.365, <jats:italic>P<\/jats:italic><jats:sub>cohort2<\/jats:sub> = 0.525, <jats:italic>P<\/jats:italic><jats:sub>cohort3<\/jats:sub> = 0.117). The reverse MR analysis indicated insufficient evidence of PD causing decreased vitamin D levels (<jats:italic>P<\/jats:italic> = 0.776).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This is the first study to use bidirectional MR across three PD cohorts to investigate the causal relationship between vitamin D and PD. The results indicate that vitamin D levels are not significantly causally related to PD risk at the genetic level. Therefore, future studies should exercise caution when investigating the relationship between vitamin D levels and PD risk. While no direct causal link exists between vitamin D levels and PD, this does not preclude the potential of vitamin D levels as a biomarker for PD diagnosis. Furthermore, larger-scale longitudinal studies are necessary to evaluate the diagnostic and predictive value of vitamin D levels in PD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0313631","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T18:29:32Z","timestamp":1731695372000},"page":"e0313631","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["No association between genetically predicted vitamin D levels and Parkinson\u2019s disease"],"prefix":"10.1371","volume":"19","author":[{"given":"Zihao","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfa","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-0500","authenticated-orcid":true,"given":"Xinling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"pone.0313631.ref001","article-title":"Impulse Control Disorders in Parkinson\u2019s Disease: An Overview of Risk Factors, Pathogenesis and Pharmacological Management","author":"F Carbone","year":"2024","journal-title":"CNS Drugs"},{"key":"pone.0313631.ref002","article-title":"The Body, the Brain, the Environment, and Parkinson\u2019s Disease","author":"ER Dorsey","year":"2024","journal-title":"J Parkinsons Dis"},{"key":"pone.0313631.ref003","article-title":"Motor Complications in Parkinson\u2019s Disease: Results from 3343 Patients Followed for up to 12\u2009Years.","author":"SE Gandhi","year":"2024","journal-title":"Mov Disord Clin Pract"},{"key":"pone.0313631.ref004","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3390\/ijms25010498","article-title":"Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks.","volume":"25","author":"KA Jellinger","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0313631.ref005","first-page":"237","article-title":"The association between vitamin D and symptom domains in psychotic disorders: A systematic review","year":"2021","journal-title":"Schizophrenia research"},{"key":"pone.0313631.ref006","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.3390\/ijms19082245","article-title":"Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact.","volume":"19","author":"R Moretti","year":"2018","journal-title":"Int J Mol Sci"},{"key":"pone.0313631.ref007","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3390\/ijms24010087","article-title":"Vitamin D in Neurological Diseases","volume":"24","author":"D Plantone","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0313631.ref008","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.3233\/JAD-230214","article-title":"Vitamin D, a Secosteroid Hormone and Its Multifunctional Receptor, Vitamin D Receptor, in Alzheimer\u2019s Type Neurodegeneration","volume":"95","author":"D Gezen-Ak","year":"2023","journal-title":"J Alzheimers Dis"},{"key":"pone.0313631.ref009","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.2147\/NDT.S407731","article-title":"The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders","volume":"19","author":"X Ye","year":"2023","journal-title":"Neuropsychiatr Dis Treat."},{"key":"pone.0313631.ref010","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.3390\/nu15173802","article-title":"Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.","volume":"15","author":"T-B Chen","year":"2023","journal-title":"Nutrients"},{"key":"pone.0313631.ref011","doi-asserted-by":"crossref","first-page":"dgae156","DOI":"10.1210\/clinem\/dgae156","article-title":"Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism","author":"Z Shahidzadeh Yazdi","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"pone.0313631.ref012","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3389\/fneur.2018.00909","article-title":"Association Between Serum Vitamin D Levels and Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis.","volume":"9","author":"X Luo","year":"2018","journal-title":"Front Neurol"},{"key":"pone.0313631.ref013","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/1028415X.2018.1493807","article-title":"Are the protective benefits of vitamin D in neurodegenerative disease dependent on route of administration? 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Ma","year":"2021","journal-title":"Biomedicines"},{"key":"pone.0313631.ref026","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.1038\/s41598-024-59090-8","article-title":"Plasminogen degrades \u03b1-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson\u2019s disease","volume":"14","author":"C Guo","year":"2024","journal-title":"Sci Rep"},{"key":"pone.0313631.ref027","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1001\/archneurol.2010.120","article-title":"Serum vitamin D and the risk of Parkinson disease","volume":"67","author":"P Knekt","year":"2010","journal-title":"Arch Neurol"},{"key":"pone.0313631.ref028","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.neulet.2019.02.018","article-title":"Vitamin D receptor polymorphisms and the susceptibility of Parkinson\u2019s disease","volume":"699","author":"X Wang","year":"2019","journal-title":"Neurosci 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Disord"},{"key":"pone.0313631.ref032","doi-asserted-by":"crossref","first-page":"112111","DOI":"10.1016\/j.exger.2023.112111","article-title":"Cross-sectional study and bioinformatics analysis to reveal the correlations of osteoporosis in patients with Parkinson\u2019s disease","volume":"173","author":"C Ma","year":"2023","journal-title":"Exp Gerontol"},{"key":"pone.0313631.ref033","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nrneurol.2014.265","article-title":"Parkinson disease. Reduced level of dietary vitamin D is associated with PD.","volume":"11","author":"I. Fyfe","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"pone.0313631.ref034","doi-asserted-by":"crossref","first-page":"e0203637","DOI":"10.1371\/journal.pone.0203637","article-title":"A randomized, controlled pilot study of the effects of vitamin D supplementation on balance in Parkinson\u2019s disease: Does age matter?","volume":"13","author":"AL Hiller","year":"2018","journal-title":"PLoS One"},{"key":"pone.0313631.ref035","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.parkreldis.2009.02.009","article-title":"Osteoporosis in Parkinson\u2019s disease","volume":"15","author":"M Invernizzi","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"pone.0313631.ref036","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/mds.24016","article-title":"25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson\u2019s disease","volume":"27","author":"M Suzuki","year":"2012","journal-title":"Mov Disord"},{"key":"pone.0313631.ref037","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1001\/archneurol.2011.30","article-title":"High prevalence of hypovitaminosis D status in patients with early Parkinson disease","volume":"68","author":"ML Evatt","year":"2011","journal-title":"Arch Neurol"},{"key":"pone.0313631.ref038","first-page":"127","article-title":"No Vitamin D Deficiency in Patients with Parkinson\u2019s Disease","volume":"12","author":"W Kuhn","year":"2022","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"pone.0313631.ref039","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neulet.2013.12.053","article-title":"The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson\u2019s disease in the Faroe Islands","volume":"561","author":"MS Petersen","year":"2014","journal-title":"Neurosci 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Qiu","year":"2019","journal-title":"Front Neurol."},{"key":"pone.0313631.ref043","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/mds.22013","article-title":"Low LDL cholesterol and increased risk of Parkinson\u2019s disease: prospective results from Honolulu-Asia Aging Study","volume":"23","author":"X Huang","year":"2008","journal-title":"Mov Disord"},{"key":"pone.0313631.ref044","doi-asserted-by":"crossref","first-page":"237","DOI":"10.14336\/AD.2015.1030","article-title":"Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson\u2019s Disease","volume":"7","author":"NW Sterling","year":"2016","journal-title":"Aging Dis"},{"key":"pone.0313631.ref045","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fnagi.2020.00053","article-title":"Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson\u2019s 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