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No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study
Author(s) -
Larsson Susanna C.,
Singleton Andrew B.,
Nalls Mike A.,
Richards J. Brent
Publication year - 2017
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27069
Subject(s) - mendelian randomization , odds ratio , single nucleotide polymorphism , vitamin d and neurology , confidence interval , confounding , medicine , genetics , oncology , biology , genotype , gene , genetic variants
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