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No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.ORCID iD: 0000-0003-0118-0341
2017 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 8, p. 1249-1252Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation.

METHODS: As instrumental variables for the Mendelian randomization analysis, we used 4 single-nucleotide polymorphisms that affect 25-hydroxyvitamin D concentrations (rs2282679 in GC, rs12785878 near DHCR7, rs10741657 near CYP2R1, and rs6013897 near CYP24A1). Summary effect size estimates of the 4 single-nucleotide polymorphisms on PD were obtained from the International Parkinson's Disease Genomics Consortium (including 5333 PD cases and 12,019 controls). The estimates of the 4 single-nucleotide polymorphisms were combined using an inverse-variance weighted meta-analysis.

RESULTS: Of the 4 single-nucleotide polymorphisms associated with 25-hydroxyvitamin D concentrations, one (rs6013897 in CYP24A1) was associated with PD (odds ratio per 25-hydroxyvitamin D-decreasing allele, 1.09; 95% confidence interval, 1.02-1.16; P = 0.008), whereas no association was observed with the other 3 single-nucleotide polymorphisms (P > 0.23). The odds ratio of PD per genetically predicted 10% lower 25-hydroxyvitamin D concentration, based on the 4 single-nucleotide polymorphisms, was 0.98 (95% confidence interval, 0.93-1.04; P = 0.56).

CONCLUSIONS: This Mendelian randomization study provides no clear support that lowered 25-hydroxyvitamin D concentration is causally associated with risk of PD. © 2017 International Parkinson and Movement Disorder Society.

Place, publisher, year, edition, pages
2017. Vol. 32, no 8, p. 1249-1252
Keywords [en]
Mendelian randomization, Parkinson's disease, vitamin D
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-397279DOI: 10.1002/mds.27069PubMedID: 28594127OAI: oai:DiVA.org:uu-397279DiVA, id: diva2:1371185
Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2020-01-16Bibliographically approved

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Larsson, Susanna C.

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