Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans

J Clin Periodontol. 2021 Nov;48(11):1404-1413. doi: 10.1111/jcpe.13538. Epub 2021 Sep 13.


Aims: 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.

Materials and methods: 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.

Results: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13).

Conclusions: 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.

Keywords: alveolar bone loss; gene × sex interaction; genetic risk; heritability; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggressive Periodontitis* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • RNA-Binding Proteins
  • Risk Factors
  • Sex Factors*
  • White People


  • CPEB4 protein, human
  • RNA-Binding Proteins