Sex‐specific genetic factors affect the risk of early‐onset periodontitis in <scp>Europeans</scp>

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  • Sandra Freitag‐Wolf
    Institute of Medical Informatics and Statistics, Kiel University University Hospital Schleswig‐Holstein Kiel Germany
  • Matthias Munz
    Department of Periodontology, Oral Medicine and Oral Surgery Charité – University Medicine Berlin, Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences Berlin Germany
  • Olaf Junge
    Institute of Medical Informatics and Statistics, Kiel University University Hospital Schleswig‐Holstein Kiel Germany
  • Christian Graetz
    Department of Conservative Dentistry, Unit of Periodontology University Medical Center Schleswig‐Holstein, Campus Kiel Kiel Germany
  • Yvonne Jockel‐Schneider
    Department of Periodontology, Clinic of Preventive Dentistry and Periodontology University Medical Center of the Julius‐Maximilians‐University Würzburg Germany
  • Ingmar Staufenbiel
    Department of Conservative Dentistry, Periodontology and Preventive Dentistry Hannover Medical School Hannover Germany
  • Corinna Bruckmann
    Department of Conservative Dentistry and Periodontology, School of Dentistry Medical University Vienna Vienna Austria
  • Wolfgang Lieb
    Institute of Epidemiology Christian‐Albrechts University Kiel Germany
  • Andre Franke
    Institute of Clinical Molecular Biology Christian‐Albrechts University Kiel Germany
  • Bruno G. Loos
    Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam Amsterdam The Netherlands
  • Søren Jepsen
    Department of Periodontology, Operative and Preventive Dentistry University of Bonn Bonn Germany
  • Henrik Dommisch
    Department of Periodontology, Oral Medicine and Oral Surgery Charité – University Medicine Berlin, Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences Berlin Germany
  • Arne S. Schaefer
    Department of Periodontology, Oral Medicine and Oral Surgery Charité – University Medicine Berlin, Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences Berlin Germany

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Various studies have reported that young European women are more likely to develop early‐onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype‐by‐sex (G × S) interactions contribute to the increased prevalence and severity.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>Using the case‐only design, we tested for differences in genetic effects between men and women in 896 North‐West European early‐onset cases, using imputed genotypes from the OmniExpress genotyping array. Population‐representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 20 loci indicated G × S associations (<jats:italic>P</jats:italic> < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (<jats:italic>ABLIM2</jats:italic>, <jats:italic>CDH13</jats:italic>, and <jats:italic>NELL1</jats:italic>). We also found independent G × S interactions of the related gene paralogs <jats:italic>MACROD1/FLRT1</jats:italic> (chr11) and <jats:italic>MACROD2/FLRT3</jats:italic> (chr20). G × S‐associated SNPs at <jats:italic>CPEB4</jats:italic>, <jats:italic>CDH13</jats:italic>, <jats:italic>MACROD1</jats:italic>, and <jats:italic>MECOM</jats:italic> were genome‐wide‐associated with heel bone mineral density (<jats:italic>CPEB4</jats:italic>, <jats:italic>MECOM</jats:italic>), waist‐to‐hip ratio (<jats:italic>CPEB4</jats:italic>, <jats:italic>MACROD1</jats:italic>), and blood pressure (<jats:italic>CPEB4</jats:italic>, <jats:italic>CDH13</jats:italic>).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter‐sex phenotypic variation in early‐onset periodontitis.</jats:p></jats:sec>

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