Depression, stress-related disorders and risk for dental caries and periodontitis: A bidirectional and multivariable Mendelian randomization study

Our Mendelian randomization (MR) analysis focused on investigating the bidirectional relationships between major depressive disorder (MDD), anxiety and stress-related disorder (ASRD), and dental caries as well as periodontitis. We used summary statistics from two studies: an MDD genome-wide association study (GWAS) including 135,458 cases with 344,901 controls and a Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) GWAS based on 12,655 ASRD individuals and 19,225 controls from Denmark. GWASs on dental caries and periodontitis were based on the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium. We employed different MR approaches, such as inverse-variance weighted (IVW), MR–Egger, weighted median, and MR-PRESSO, to calculate causal effects. Single-variable MR analysis revealed that ASRD was potentially significantly associated with decayed, missing, and filled tooth surfaces (DMFS) (β = 0.056; 95 % CI: 0.009, 0.103; p = 0.018). Periodontitis was suggested to be causally related to increased ASRD risk (OR = 1.143, 95 % CI: 1.008, 1.298; p = 0.038). According to the multivariable MR analysis, no significant associations were detected between MDD and ASRD with dental caries and periodontitis, and vice versa. ASRD demonstrated a potential association with DMFS, and periodontitis was found to potentially impact ASRD according to single-variable MR analysis. Nevertheless, no significant associations were identified between MDD, ASRD, dental caries, or periodontitis after adjusting for smoking status and education level. Hence, more robust genetic instruments are required to validate and reinforce our findings.