107: Host genetics of endodontic infections: FinnGen GWAS

Salminen A et al., Nature Communications - A large GWAS in 485,230 FinnGen participants (132,124 cases) identified genetic loci associated with pulpal and apical diseases. The study highlights strong signals near HORMAD2 on chromosome 22 and multiple signals in the HLA class II region, links top variants to immune and antigen-presentation pathways, and reports replication in independent cohorts. Key terms: GWAS, endodontic infections, HORMAD2, HLA, FinnGen.

Study Highlights:
A GWAS of 485,230 Finnish individuals with 132,124 cases of pulpal or apical disease identified 15 independent loci across 12 chromosomes, with strongest signals near HORMAD2 (chr22) and in the HLA class II region. Imputed HLA alleles, notably DRB1*04:01 and DQB1*03:01, were associated with endodontic infections, and many lead variants carried regulatory annotations tied to MHC class II, humoral immunity, and antigen processing. Most lead SNPs remained significant after adjusting for caries and several associations replicated in FinnGen subcohorts and the Estonian Biobank. Genetic correlations were observed with pain, caries, cardiometabolic traits and cardiovascular disease, and SNP heritability was modest (h2 ≈ 0.017–0.021).

Conclusion:
Genetic variation affecting immune regulation—particularly MHC class II/HLA alleles and regulatory variation near HORMAD2 and linked genes—contributes to susceptibility to pulpal and apical diseases and provides loci for mechanistic follow-up and risk evaluation.

Music:
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Article title:
Genome-wide association study of pulpal and apical diseases

First author:
Salminen A

Journal:
Nature Communications

DOI:
10.1038/s41467-025-61721-1

Reference:
Salminen A, Hyvärinen K, Ritari J, et al. Genome-wide association study of pulpal and apical diseases. Nature Communications (2025). DOI: 10.1038/s41467-025-61721-1

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/ep-107-gwas-pulpal-apical-diseases

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-08-15.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the main GWAS findings, mechanistic interpretation (MTMR3/autophagy, HLA region), HLA alleles, confounding adjustment (DMFS), genetic correlations, replication, and limitations described in the transcript.
- transcript topics: Scale and design of FinnGen GWAS; Genetic loci identified (HORMAD2, MTMR3, HLA region); Autophagy and MTMR3 as immune-modulating mechanism; Imputed HLA alleles DRB1*04:01 and DQB1*03:01; DMFS adjustment and independence from caries; Genetic correlations with pain, BMI, smoking, type 2 diabetes, cardiovascular disease

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- 15 independent loci associated with endodontic infections
- Strongest signal on chromosome 22 near HORMAD2/MTMR3
- Second locus in the HLA class II region with DRB1*04:01 and DQB1*03:01 associations
- MTMR3/autophagy link and its role in immune response
- Heritability estimate h2 ≈ 0.017–0.021
- DMFS adjustment shows many associations independent of caries

QC result: Pass.