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

Matthias Munz, Gesa M Richter, Bruno G Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Ilyas Ahmad, Ingmar Staufenbiel, Nathalie van der Velde, André G Uitterlinden, Lisette C P G M de Groot, Jürgen Wellmann, Klaus Berger, Bastian Krone, Per Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Jeanette Erdmann, Henrik Dommisch, Arne S Schaefer

Journal: European journal of human genetics : EJHG 2019;27(1):102-113

PMID: 30218097

Abstract

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, 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, 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.

Address: Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.; Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.; Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.; Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, USA.; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, USA.; Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, USA.; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.; Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pedodontics, Dental School, University Medicine Greifswald, Greifswald, Germany.; Department of Conservative Dentistry and Periodontology, Medical University Vienna, School of Dentistry, Vienna, Austria.; Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Würzburg, Germany.; Unit of Periodontology, Department of Conservative Dentistry, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.; Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.; Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany.; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Internal Medicine section of Geriatrics, Amsterdam Medical Center, Amsterdam, The Netherlands.; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.; Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands.; Institute of Epidemiology and Social Medicine, University Münster, Münster, Germany.; Institute of Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Essen, Germany.; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland.; Department of Medicine 1, University of Kiel, Kiel, Germany.; Institute of Epidemiology, Christian-Albrechts-University, Kiel, Germany.; Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research) partner site Hamburg/Lübeck/Kiel, 23562, Lübeck, Germany.; University Heart Center Luebeck, 23562, Lübeck, Germany.; Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. [email protected].
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