No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study

Abstract

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.

Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade

“…Examples of such markers include pesticide‐induced gene mutations and biological markers of oxidative stress . Techniques such as Mendelian randomization, whereby a genetic marker associated with the levels of a factor associated with risk such as vitamin D or serum urate can avoid error or bias associated with exposure measurements. This method can be used to corroborate findings and improve causal inference when positive.…”

Risky behaviors and Parkinson disease

“…We have also seen a surge of MR studies in the field of PD specifically exploring the causal role of several circulating biomarkers. [10][11][12][13][14][15] For example, a recent MR study reported a significant causal association with a lifelong PD risk reduction of 3% per 10-μg/dL increase in serum iron levels. 12 Most recently, another study further reported a risk reduction of 18% with a lifetime exposure of 5-kg/m 2 higher body mass index.…”

CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population

“…Moreover, our report showed that the risk effects of the rs6013897 variant were statistically significant in most subgroups, and there was no significant heterogeneity within each subgroup variable, which suggested that these variables did not modify this association. Some previous research has also reported that rs6013897 can affect the risk of Parkinson disease (PD), aggressive prostate cancer, and bone mineral density at the femoral neck (FN-BMD) by affecting the 25(OH)D 3 concentration (Dimitrakopoulou et al, 2017;Larsson et al, 2017;Larsson et al, 2018).…”