AbstractAimTo investigate the associations of tobacco smoking and alcohol consumption with periodontitis using Mendelian randomization (MR) analysis.Materials and methodsWe used 17 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for the number of cigarettes per day from a genome‐wide association study (GWAS) of 337,334 individuals, 109 SNPs for a lifetime smoking index from GWAS of 462,690 participants, and 33 SNPs for the number of drinks per week from GWAS of 941,280 individuals. The periodontitis GWAS included 12,289 cases and 22,326 controls. Wald ratios were obtained by dividing the SNP–periodontitis effects by SNP–exposure effects and pooled using an inverse‐variance weighted model.ResultsGenetic liabilities for higher number of cigarettes per day (odds ratio [OR] per one standard deviation (1SD) increment = 1.56; 95% CI: 1.18–2.07, p‐value = .0018, Q‐value = .0054), lifetime smoking index (OR per 1SD = 1.26; 95% CI: 1.04–1.53, p‐value = .0161, Q‐value = .0242), and drinks per week (OR per 1SD = 1.41; 95% CI: 1.04–1.90, p‐value = .0265, Q‐value = .0265) were associated with increased odds of periodontitis. Estimates were consistent across robust and multivariable MR analyses.ConclusionsThe findings of this MR analysis suggest an association between tobacco smoking and alcohol consumption with periodontitis.