AbstractAimEpidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.Materials and MethodsForty‐seven risk genes of genome‐wide significance of RA and SLE were genotyped in a German case–control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.ResultsVariants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6–6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6–0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta‐interferon signalling and are also genome‐wide associated with SLE and inflammatory bowel disease.ConclusionThe study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.