Mendelian randomization highlights the causal association of obesity with periodontal diseases

Abstract

Aim The underlying mechanisms connecting obesity and periodontal diseases remain unclear. This study investigates the potential causal association of obesity with periodontal diseases using Mendelian randomization (MR). Materials and Methods Single‐nucleotide polymorphisms of obesity traits including body mass index (BMI), waist circumference (WC), and WC adjusted for BMI (WCadjBMI) from large‐scale genome‐wide association studies were screened for instrumental variables. The single trait periodontitis and the combined trait comprising periodontitis and loose teeth were adopted as surrogates for periodontal diseases. Inverse‐variance weighted (IVW), series of sensitivity analyses and multivariable MR were employed to determine the association of obesity with periodontal diseases. Results IVW results showed that per 1‐SD increment in BMI (odds ratio, OR = 1.115; 95% confidence interval [CI] = 1.064–1.169; p < .001) and WC (OR = 1.117; 95% CI = 1.052–1.185; p < .001), but not WCadjBMI, were significantly associated with an increased risk of periodontitis/loose teeth. Moreover, the MR estimates were consistent across other MR sensitivity analyses and multivariable MR. However, a causal association of obesity with the single trait periodontitis was not identified. Conclusions The presented evidence supports previous epidemiological findings by showing a potential causal association of genetic liability to obesity with periodontal diseases. The biological mechanisms underlying this association warrant further investigation.

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

“…Similarly, a recent MR study using 65 SNPs as IVs demonstrated a weak association between BMI and periodontitis (OR = 1.143, 95% CI: 0.975-1.340, p = 0.099), and a positive association between BMI and a combined trait comprising periodontitis and loose teeth (OR = 1.115, 95% CI: 1.064-1.169, p < 0.001). 31 Contrary to expectations, we found no causal relationship between gene-predicted BW and childhood BMI with periodontitis risk. Although observational studies have demonstrated that having a high BMI in early life is associated with an increased risk of periodontitis in later life, 13 our findings imply that previously observed associations are likely a result of a higher BMI persisting into adulthood.…”

“…In the current study, we utilized the findings from the latest GWAS, 11 which captured various aspects of the etiology of BMI, and resulted in a higher overall statistical power than the previous smaller MR study. Similarly, a recent MR study using 65 SNPs as IVs demonstrated a weak association between BMI and periodontitis (OR = 1.143, 95% CI: 0.975–1.340, p = 0.099), and a positive association between BMI and a combined trait comprising periodontitis and loose teeth (OR = 1.115, 95% CI: 1.064–1.169, p < 0.001) 31 …”

The Association between Obesity and Periodontal Disease: NHANES 2009-2012 Analysis.

“…Another recent MR study found a direct association between BMI and periodontitis. 23 The association between periodontal disease and body fatness is biologically plausible via several pathways. Adipose tissue can act as an active endocrine organ, and obesity is associated with increased production of inflammatory mediators such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6.…”

“…For females, the cutoff points were <71 cm, between 71-79.9 cm, between 80-88 cm, and >88cm. 23 The lowest WC category was called category 1 and the highest was called category 4.…”

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral–gut and gut–oral axes through bidirectional Mendelian randomization

“…After harmonization, we selected SNPs with P exposure < P outcome and refrained from using proxies to maintain consistency of IVs across all analyses. Furthermore, to investigate the potential IVs associated with risk factors for periodontitis, such as smoking status, alcohol consumption, body mass index, glycaemic traits and educational attainment (Baumeister et al, 2021(Baumeister et al, , 2022Dong et al, 2022), we conducted a thorough search of the PhenoScanner database (http://www.phenoscanner.medschl.cam.ac.uk/ ) and the GWAS Catalog database (https://www.ebi.ac.uk/gwas/home) to identify genetic variants significantly associated (p < 5 Â 10 À8 ) with these factors (Kamat et al, 2019;Sollis et al, 2023). Subsequently, any of these genetic variants that were used as IVs directly associated with risk factors for periodontitis were removed from the current study when analysing the causal effects of GM taxa on periodontitis, in accordance with the MR assumption (2).…”