Abdominal adiposity and periodontitis: a Mendelian randomisation study

Objectives: Mendelian randomization (MR) uses a genetic variant which is associated with an exposure as an instrumental variable to determine whether the exposure is causally related to an outcome. MR exploits the random assignment of genes as a means of reducing confounding in examining exposure-outcome associations. The aim was to investigate whether abdominal adiposity (waist circumference) is causally related to periodontitis in a group of 60-70 year old men.
Methods: The study was based on 1271 dentate men in Northern Ireland who had a comprehensive periodontal examination and provided a DNA sample. The adiposity-associated variant rs17782313 in MC4R (melanocortin-4 receptor) was used as an instrumental variable for waist circumference in a MR design. Periodontitis was classified by mean clinical attachment level (CAL). Age and smoking adjusted regression analysis was used to test for associations.
Results: There was an association between variants in rs17782313 and waist circumference (P_trend =0.02). After adjustment for age and smoking each extra C allele was associated with a 1.2 (95% confidence interval 0.3 to 2.1) cm increase in waist circumference, P=0.01. Abdominal adiposity was significantly associated with CAL, P=0.007: each 1 cm increase in WC was associated with 0.01 (95% CI 0.00 to 0.02) mm increase in CAL. However, when the instrumental variable was applied to investigate the effect of WC on CAL the association was not significant, P=0.44: each 1 cm increase in WC mediated through genotype was associated with -0.04 (95% CI -0.14 to 0.06) mm increase in CAL.
Conclusions: Mendelian randomisation did not support a causal relationship between abdominal adiposity and periodontitis via the instrumental variable method applied.