Year: 2018
Type: article
Abstract: Periodontitis is one of the most common inflammatory human diseases with a strong genetic component. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWASs) of chronic periodontitis (CP) have largely been unsuccessful in identifying common susceptibility factors. A combination of quantitative trait loci (QTL) mapping in mice with association studies in humans has the potential to discover novel risk loci. To this end, we assessed alveolar bone loss in response to experimental periodontal infection in 25 lines (286 mice) from the Collaborative Cross (CC) mouse population using micro-computed tomography (µCT) analysis. The orthologous human chromosomal regions of the significant QTL were analyzed for association using imputed genotype data (OmniExpress BeadChip arrays) derived from case-control samples of aggressive periodontitis (AgP; 896 cases, 7,104 controls) and chronic periodontitis (CP; 2,746 cases, 1,864 controls) of northwest European and European American descent, respectively. In the mouse genome, QTL mapping revealed 2 significant loci (-log P = 5.3; false discovery rate = 0.06) on chromosomes 1 ( Perio3) and 14 ( Perio4). The mapping resolution ranged from ~1.5 to 3 Mb. Perio3 overlaps with a previously reported QTL associated with residual bone volume in F2 cross and includes the murine gene Ccdc121. Its human orthologue showed previously a nominal significant association with CP in humans. Use of variation data from the genomes of the CC founder strains further refined the QTL and suggested 7 candidate genes ( CAPN8, DUSP23, PCDH17, SNORA17, PCDH9, LECT1, and LECT2). We found no evidence of association of these candidates with the human orthologues. In conclusion, the CC populations enabled mapping of confined QTL that confer susceptibility to alveolar bone loss in mice and larger human phenotype-genotype samples and additional expression data from gingival tissues are likely required to identify true positive signals.
Source: Journal of Dental Research
Authors: A. Nashef, R. Qabaja, Y. Salaymeh, M. Botzman, M. Munz, H. Dommisch, B. Krone, P. Hoffmann, J. Wellmann, M. Laudes, K. Berger, T. Kocher, B. Loos, N. van der Velde, A.G. Uitterlinden, L.C.P.G.M. de Groot, A. Franke, S. Offenbacher, W. Lieb, K. Divaris, R. Mott, I. Gat-Viks, E. Wiess, A. Schaefer, F.A. Iraqi, Y.H. Haddad
Institutions: Hebrew University of Jerusalem, Tel Aviv University, Institute for Integrative and Experimental Genomics, Charité – Universitätsmedizin Berlin, University of Lübeck, Institut für Medizinische Informatik, Biometrie und Epidemiologie, University of Bonn, University Hospital of Basel, University of Münster, University Hospital Schleswig-Holstein, Universitätsmedizin Greifswald, Universität Greifswald, Academic Center for Dentistry Amsterdam, University of Amsterdam, Erasmus MC, Amsterdam University Medical Centers, Amsterdam Public Health, Amsterdam UMC Location Vrije Universiteit Amsterdam, Christian-Albrechts-Universität zu Kiel, University of North Carolina at Chapel Hill, University College London
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: bronze
Funders: Pfizer, AstraZeneca, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Westfälische Wilhelms-Universität Münster, Deutsches Zentrum für Neurodegenerative Erkrankungen, Federalno Ministarstvo Obrazovanja i Nauke, Deutsche Migräne- und Kopfschmerzgesellschaft e.V., Heinz Nixdorf Stiftung, National Institutes of Health, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, Cilag
Awards: G1916810480, G2207173938, Verbundprojekt: Nationales Genomforschungsnetz 2: Systematisch-Methodische Plattform GEM: Standort Kiel: PopGen: Populationsrepräsentative Biobank Schleswig-Holstein, G2396948287, G2929324288, G2950734072, G3041445225, AgroClustEr: FoCus - Food Chain Plus. Verbund Gesundheitliche Bewertung und Konsumentenverhalten., North Carolina Translational & Clinical Sciences Institute (NC TraCS), Die bidirektionale Analyse der Beziehung zwischen subklinischer Arteriosklerose und der Depression (BiDirect), Training Program for the Next Generation of Oral Health Researches (NextGen), G4806685284, G49395674, G5367459596, GENOME-WIDE ASSOCIATION STUDY OF PERIODONTAL DISEASE, G7660237446
OpenAlex ID: W2782388955