A1 Refereed original research article in a scientific journal
Genetic Loci Associated With Periodontitis: The FinnGen Study Based on National Health Registers
Authors: Salminen, Aino; Hyvärinen, Kati; Ritari, Jarmo; Caetano, Ana; Kambur, Oleg; Mäntylä, Päivi; Yilmaz, Mustafa; Sinisalo, Juha; FinnGen; Perola, Markus; Havulinna, Aki; Nibali, Luigi; Gürsoy, Ulvi Kahraman; Pussinen, Pirkko J.
Publisher: Wiley-Blackwell
Publication year: 2025
Journal: Journal of Clinical Periodontology
Article number: jcpe.14193
Volume: 52
Issue: 9
ISSN: 0303-6979
eISSN: 1600-051X
DOI: https://doi.org/10.1111/jcpe.14193
Web address : https://onlinelibrary.wiley.com/doi/10.1111/jcpe.14193
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499411301
Aim
To perform a genome-wide association study (GWAS) for periodontitis in the FinnGen cohort, as genetic factors contribute to periodontitis.
Materials and Methods
We included nearly 250,000 Finnish individuals who had visited a dentist in the public healthcare sector for a clinical oral examination. We designed three periodontitis phenotypes based on diagnosis and procedure codes and CPI indexes in national health registers.
Results
We identified 11 independent genetic loci associated with periodontitis, among which 6 were common and novel. A locus near the FST gene was associated with two phenotypes, whereas other lead SNPs were located near ARL15, MFHAS1, DEFB130A and APOE. Additionally, all phenotypes in the discovery and replication cohorts were associated with genetic variations in the HLA region. Furthermore, imputed HLA allele frequencies identified independent associations between HLA-DRB1, HLA-DPB1 and HLA-DQA1 and periodontitis. Based on single-cell RNA sequencing, the expression of genes near our lead SNPs across all three phenotypes was particularly enriched in gingival cell lineages important in the pathogenesis of periodontitis. Phenotypical and genetic correlations revealed associations between periodontitis and bacterial diseases, as well as autoimmune and cardiometabolic phenotypes.
Conclusions
Our GWAS suggests that genetic variation contributing to immune dysregulation is involved in the pathogenesis of periodontitis, which has considerable genetic similarity with other complex traits.
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Funding information in the publication:
The research group was supported by grants from the Academy of Finland, the Sigrid Juselius Foundation, Finnish Dental Society Apollonia,Novo Nordisk Foundation, Paulo Foundation and Finnish Foundation for Cardiovascular Research. The FinnGen project is funded by two grants fromBusiness Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd., Biogen MA Inc.,Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LLC, Pfizer Inc., GlaxoSmithKlineIntellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc., Novartis AG and Boehringer IngelheimInternational GmbH.