Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci


Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

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This work was supported by a research grant of the German Research Foundation DFG (Deutsche Forschungsgemeinschaft; GZ: SCHA 1582/3-1). Collection of the AgP cases was additionally supported by the German Ministry of Education and Research through the POPGEN biobank project (01GR0468). The Dortmund Health Study (DHS) is supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp and Dohme and Pfizer to the University of Muenster (collection of sociodemographic and clinical data). Blood collection in the Dortmund Health Study was done through funds from the Institute of Epidemiology and Social Medicine University of Muenster and genotyping supported by the German Ministry of Research and Education (BMBF, grant no. 01ER0816). FOCUS was supported by the Federal Ministry of Education and Research BMBF (FKZ 0315540 A). The HNR study is supported by the Heinz Nixdorf Foundation (Germany). Additionally, the HNR study was funded by the German Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). The genotyping of the Illumina HumanOmni-1 Quad BeadChips of the HNR subjects was financed by the German Centre for Neurodegenerative Diseases (DZNE), Bonn. SHIP is part of the Community Medicine Research net ( of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Generation of genome-wide SNP data has been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg, West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH.

Authors contribution

MM, SO, TK, AU, LdG, JE, and AS where involved in the study design. GR, BL, KD, SO, AT, BH, TK, CB, YJS, CG, IS, NV, AU, LdG, JW, KB, BK, PH, ML, WL, AF, HD, JE, and AS managed the studies. BL, SJ, SO, BH, TK, CB, YJS, CG, IS, NV, AU, LdG, JW, KB, BK, PH, HD, JE, and AS were involved in the subject recruitment. SO, AT, CG, ML, WL, AF, and AS were involved in the genotyping. MM applied the methods and did the analysis. MM, GR, and AS did the interpretation of the results. MM did the drafting of the manuscript. GR, BL, KD, AT, IA, BH, WL, JE, and AS were involved in the critical review of the manuscript.

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Correspondence to Arne S. Schaefer.

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