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Genome-wide association study of pulpal and apical diseases

Author

Listed:
  • Aino Salminen

    (University of Helsinki and Helsinki University Hospital)

  • Kati Hyvärinen

    (Research and Development)

  • Jarmo Ritari

    (Research and Development)

  • Jussi M. Leppilahti

    (University of Oulu
    Oulu University Hospital
    Oulu University Hospital and University of Oulu)

  • Ulla Palotie

    (University of Helsinki and Helsinki University Hospital)

  • Ville Vuollo

    (University of Oulu
    Oulu University Hospital and University of Oulu)

  • Oleg Kambur

    (Finnish Institute for Health and Welfare
    University of Eastern Finland
    University of Turku
    University of Helsinki)

  • Kadri Reis

    (University of Tartu)

  • Anu Reigo

    (University of Tartu)

  • Priit Palta

    (University of Tartu)

  • Markus Perola

    (Finnish Institute for Health and Welfare)

  • Juha Sinisalo

    (Helsinki University Hospital and University of Helsinki)

  • Aki S. Havulinna

    (Finnish Institute for Health and Welfare
    University of Helsinki
    University of Turku)

  • Päivi Mäntylä

    (University of Eastern Finland)

  • Ulvi Kahraman Gürsoy

    (University of Turku)

  • A. Liisa Suominen

    (University of Eastern Finland
    Kuopio University Hospital)

  • David P. Rice

    (University of Helsinki and Helsinki University Hospital)

  • Vuokko Anttonen

    (University of Oulu)

  • Pekka Nieminen

    (University of Helsinki and Helsinki University Hospital)

  • Pirkko J. Pussinen

    (University of Helsinki and Helsinki University Hospital
    University of Eastern Finland)

Abstract

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.

Suggested Citation

  • Aino Salminen & Kati Hyvärinen & Jarmo Ritari & Jussi M. Leppilahti & Ulla Palotie & Ville Vuollo & Oleg Kambur & Kadri Reis & Anu Reigo & Priit Palta & Markus Perola & Juha Sinisalo & Aki S. Havulinn, 2025. "Genome-wide association study of pulpal and apical diseases," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61721-1
    DOI: 10.1038/s41467-025-61721-1
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    References listed on IDEAS

    as
    1. Triin Laisk & Maarja Lepamets & Mariann Koel & Erik Abner & Reedik Mägi, 2021. "Genome-wide association study identifies five risk loci for pernicious anemia," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    2. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    3. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
    Full references (including those not matched with items on IDEAS)

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