The causal effect of life course adiposity on periodontitis: A Mendelian randomization study.

Abstract

To establish whether life course adiposity, including birth weight (BW), childhood and adulthood body mass index (BMI), waist-hip ratio (WHR), and body fat percentage (BF%), has a causal influence on periodontitis. We used single-nucleotide polymorphisms with significant associations with life course adiposity as instrumental variables. We examined their association with periodontitis risk in a genome-wide association study involving periodontitis cases (n=17,353) and healthy controls (n=28,210) using a two-sample Mendelian randomization (MR) strategy. The association of life course adiposity with periodontitis risk was estimated with inverse-variance weighting with random effects. We performed sensitivity analyses using MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger methods. We calculated the odds ratios (ORs) for one standard deviation (SD) increase per risk factor to estimate the effect on the risk of periodontitis. After correction for multiple testing, there was an association between each SD increase in gene-predicted adulthood BMI with a higher periodontitis risk (OR=1.15, 95% confidence interval [CI]: 1.06-1.23, p =3.1×10-4), with a similar influence for BF% on periodontitis risk (OR=1.29, 95% CI: 1.12-1.49, p =3.3×10-4). No causal association was detected for gene-predicted BW, childhood BMI, or WHR with periodontitis risk. We present new proof supporting a causal function of greater adiposity, especially high BMI and BF%, being associated with higher periodontitis risk. We recommend that future studies focus on periodontitis from a life course perspective.