Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1404-1413 |
| Number of pages | 10 |
| Journal | Journal of Clinical Periodontology |
| Volume | 48 |
| Issue number | 11 |
| Early online date | 18 Aug 2021 |
| DOIs | |
| Publication status | Published - Nov 2021 |
Bibliographical note
© 2021 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.Funding
The authors thank the participants and staff of the health professionals. This work was supported by the research grant SCHA 1582/3‐1 of the German Research Foundation DFG. SFW was supported by grants from the German Research Foundation Excellence Cluster “Inflammation at Interfaces” (EXC306, EXC306/2). Collection of the cases was additionally supported by the German Ministry of Education and Research through the POPGEN biobank project (01GR0468).
| Funders | Funder number |
|---|---|
| German Research Foundation Excellence Cluster “Inflammation at Interfaces | EXC306/2, EXC306 |
| Deutsche Forschungsgemeinschaft | |
| Bundesministerium für Bildung und Forschung | 01GR0468 |
