A Mendelian randomization study on the effect of 25‐hydroxyvitamin D levels on periodontitis

Abstract

Background: Twenty five-hydroxy vitamin D (25OHD) levels have been proposed to protect against periodontitis based on in vitro and observational studies but evidence from long-term randomized controlled trials (RCTs) is lacking. This study tested whether genetically proxied 25OHD is associated with periodontitis using Mendelian randomization (MR).Methods: Genetic variants strongly associated with 25OHD in a genome-wide association study (GWAS) of 417,580 participants of European ancestry were used as instrumental variables, and linked to GWAS summary data of 17,353 periodontitis cases and 28,210 controls. In addition to the main analysis using an inverse variance weighted (IVW) model, we applied additional robust methods to control for pleiotropy. We also undertook sensitivity analyses excluding single nucleotide polymorphisms (SNPs) used as instruments with potential pleiotropic effects and used a second 25OHD GWAS for replication. We identified 288 SNPs to be genome-wide significant for 25OHD, explaining 7.0% of the variance of 25OHD levels and providing ≥90% power to detect an odds ratio (OR) of ≤ 0.97. Results: MR analysis suggested that a 1 standard deviation increase in natural log-transformed 25OHD was not associated with periodontitis risk (IVW OR = 1.04; 95% confidence interval (CI): 0.97-1.12; P-value = 0.297). The robust models, replication, and sensitivity analyses were coherent with the primary analysis.

Association between circulating 25‐hydroxyvitamin D metabolites and periodontitis: Results from the NHANES 2009–2012 and Mendelian randomization study

“…However, in contrast to the observational findings, our present wide‐ranging MR study did not support the association between 25(OH)D and periodontitis risk. Our results confirm the recent MR findings that no causal link is present between 25(OH)D and periodontitis (Baumeister et al, 2021). And the recent MR study of the causal relationship between vitamin D and periodontitis supports our conclusions (Z. Hu et al, 2022).…”

Serum levels of vitamin D and periodontal inflammation in community‐dwelling older Japanese adults: The Otassha Study

“…It should be noted that recent MR studies (Baumeister et al, 2022; Hu et al, 2022; Li et al, 2022) did not show a causal association between serum 25(OH)D and periodontitis. There are several potential explanations for the inconsistency between the results of our study and those of recent MR studies.…”

“…First, previous studies with MR analysis did not include a sufficient number of Asian populations; therefore, the results may not be applicable to our study population of Japanese adults. Second, previous studies used the linear MR method (Baumeister et al, 2022; Hu et al, 2022; Li et al, 2022). Therefore, if the causal effect of vitamin D is truly non‐linear and restricted to the low 25(OH)D range, as suggested by our current analyses, previous studies with the linear MR method could not have captured this threshold effect.…”

“…First, previous studies with MR analysis did not include a sufficient number of Asian populations; therefore, the results may not be applicable to our study population of Japanese adults. Second, previous studies used the linear MR method (Baumeister et al, 2022;Hu et al, 2022;Li et al, 2022).…”

Dietary vitamin D and calcium and periodontitis: A population-based study

“…Other factors that may explain the lack of consistent results regarding the association between vitamin D, calcium, and periodontitis relate to the assessment of the micronutrients. In a study using Mendelian randomization, the authors did not find an association between 25(OH)D serum levels and periodontitis in a sample of approximately 45,000 Europeans ( 41 ). While that study corroborates our findings regarding the lack of association between vitamin D intake and periodontitis, the authors did not use the information on calcium.…”