A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genome-wide association study of pulpal and apical diseases
Tekijät: Salminen, Aino; Hyvärinen, Kati; Ritari, Jarmo; Leppilahti, Jussi M.; Palotie, Ulla; Vuollo, Ville; Kambur, Oleg; FinnGen; Estonian Biobank Research Team; Reis, Kadri; Reigo, Anu; Palta, Priit; Perola, Markus; Sinisalo, Juha; Havulinna, Aki S.; Mäntylä, Päivi; Gürsoy, Ulvi Kahraman; Suominen, A. Liisa; Rice, David P.; Anttonen, Vuokko; Nieminen, Pekka; Pussinen, Pirkko J.; FinnGen; Estonian Biobank Research Team
Kustantaja: Springer Nature
Julkaisuvuosi: 2025
Journal: Nature Communications
Tietokannassa oleva lehden nimi: Nature Communications
Artikkelin numero: 6774
Vuosikerta: 16
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-025-61721-1
Verkko-osoite: https://doi.org/10.1038/s41467-025-61721-1
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/499673865
Infections of the dental pulp are common sequelae of microbial activity and host susceptibility, affecting >80% of adult population. We performed a genome-wide association study on endodontic infections utilizing Finnish health registry and genotype data from FinnGen. Cases [132,124 (27.2%)] had at least one ICD10-diagnosis code of pulpal or apical diseases, whereas 353,106 individuals without diagnoses served as controls. We investigated two clinical sub-phenotypes, Pulpitis and Necrosis of pulp or apical periodontitis. Our analysis resulted in significant associations in 12 chromosomes and 15 independent loci, such as those near HORMAD2 gene and those in the HLA region. The imputed HLA alleles, especially DRB1 * 04:01 and DQB1 * 03:01, were associated with endodontic infections. Bioinformatic analysis of the top variants indicated several potential regulatory variants which are involved in MHC class II protein complex, humoral immune responses, and antigen processing. Our study widens understanding on how immune dysregulation resulting from immunogenetic variation is involved in the pathogenesis of endodontic infections.
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Julkaisussa olevat rahoitustiedot:
We want to acknowledge the participants and investigators of the FinnGen study. A full list of FinnGen Consortium members is shown in the Supplementary Data 6. The FinnGen project is funded by two grants from Business 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 Inc. (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Johnson&Johnson Innovative Medicine Inc., Novartis AG, Boehringer Ingelheim International GmbH and Bayer AG. Following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta), Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki/) and Arctic Biobank (https://www.oulu.fi/en/university/faculties-and-units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank). All Finnish Biobanks are members of BBMRI.fi infrastructure (https://www.bbmri-eric.eu/national-nodes/finland/). Finnish Biobank Cooperative FINBB is the coordinator of BBMRI-ERIC operations in Finland. The Finnish biobank data can be accessed through the Fingenious® services (https://site.fingenious.fi/en/) managed by FINBB. We want to acknowledge the participants of the Estonian Biobank for their contributions. The Estonian Genome Center analyses were partially carried out in the High Performance Computing Center, University of Tartu. We acknowledge the Estonian Biobank Research Team (Andres Metspalu, Mari Nelis, Lili Milani, Reedik Mägi, Georgi Hudjashov, Tõnu Esko; estbbresearch@ut.ee) for data collection, genotyping, QC, and imputation. NFBC1966 46 year follow-up study received financial support from University of Oulu Grant no. 24000692, Oulu University Hospital Grant no. 24301140, and ERDF European Regional Development Fund Grant no. 539/2010 A31592. NFBC1986 33−35 year follow-up study received financial support from University of Oulu (Strategic funding from donations) and Oulu University Hospital (K65760). The oral health study was supported in part by the Research Council of Finland (former Academy of Finland, #326189). The work was supported by the Research Council of Finland (#340750 to P.J.P. and #326189 to J.M.L. and V.V.), Sigrid Juselius foundation (P.J.P.), Novo Nordisk fonden (P.J.P.), Paulo foundation (P.J.P.), Selma and Maja-Lisa Selander foundation (A.S. and P.J.P.), HUS Helsinki University Hospital Research Foundation (#Y2519SU008 to D.P.R.), and the Estonian Research Council (#PRG1291 to K.R., A.R., and P.P.). Open access was funded by Helsinki University Library.
