Non-Cochrane · aetiology · PM39192244
Genome-wide association meta-analysis identifies two novel loci associated with dental caries.
Nogawa Shun, Morishita Satoru, Saito Kenji, et al. · BMC oral health · 2024 · PubMed · doi:10.1186/s12903-024-04799-1
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
8
current version
GRADE rated
0
No studies
0
Included studies
1
linked below
No studies 0 · 0%Ungraded 8 · 100%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults (>=18 years): present-study Japanese direct-to-consumer participants and European/Japanese cohorts from a previously reported GWAS; self-reported dental caries and periodontal disease | 45,525 Japanese individuals (dental caries: 30,859 cases/14,666 controls; periodontal disease: 7,059 cases/38,466 controls) plus GLIDE, UKB and BBJ cohorts via the previously reported GWAS |
| Intervention | Genome-wide common genetic variants (additive dosage; ~8.3 million imputed variants); germline genotype | Two novel dental-caries loci: rs10974056 (GLIS3) and rs4801882 (SIGLEC5); gene-based ADGRL2 (FDR q<0.05) |
| Comparison | Non-effect allele; genome-wide significance threshold (P<5E-8) | Non-effect allele; genome-wide significance P<5E-8 |
| Outcomes | Dental caries and periodontal disease (self-reported; the prior GWAS used DMFS/dentures for caries and periodontitis/loose teeth for periodontal disease) | Dental caries: 2 novel loci reached genome-wide significance after meta-analysis. Periodontal disease: no novel loci (only previously known; chr19/SIGLEC5 not replicated in Japanese). SNP heritability h2=0.0258 (caries), 0.0519 (periodontal disease) |
| Study designs | Population-based genetic epidemiology (direct-to-consumer genetic testing cohorts; consortium/biobank GWAS) | Japanese direct-to-consumer cohort + European/Japanese consortium GWAS |
| Timing | Lifelong (germline genotype) | Lifelong (germline genotype) |
Search date: Not applicable (primary GWAS with meta-analysis of one previously published GWAS; no systematic literature search). Databases: GWAS datasets: present study (Genequest ALL, Euglena MyHealth, HealthData Lab; 45,525 Japanese direct-to-consumer participants); previously reported GWAS (Shungin 2019) combining GLIDE consortium, UK Biobank (UKB) and BioBank Japan (BBJ)
Questions and results
rs10974056 effect allele A (intron variant in GLIS3, chr9:3,889,264) vs Non-effect allele C
Population: Adults from Japanese and European cohorts (present-study Japanese direct-to-consumer cohort + GLIDE consortium and UK Biobank European cohorts); self-reported dental caries cases vs controls
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Dental caries (meta of mixed phenotypes: present-study self-report + GLIDE clinical DMFS + UKB self-report/dentures) Lifelong (germline genotype) · Meta-analysis: present study + GLIDE + UKB Meta-analysis identified a novel genome-wide-significant locus for dental caries at rs10974056 in GLIS3 (P=3.93E-08); ungraded. Source: Table 2; Results 'Genome-wide association analysis of dental caries and periodontal disease'; Fig. 1a; Fig. 2a · same question in other reviews | Z-score (meta) -5.494 | 3 studies · 533348 participants | Ungraded |
rs4801882 effect allele G (intron variant in SIGLEC5, chr19:52,127,053) vs Non-effect allele A
Population: Adults from Japanese and European cohorts (present-study Japanese direct-to-consumer cohort + GLIDE consortium and UK Biobank European cohorts); self-reported dental caries cases vs controls
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Dental caries (meta of mixed phenotypes: present-study self-report + GLIDE clinical DMFS + UKB self-report/dentures) Lifelong (germline genotype) · Meta-analysis: present study + GLIDE + UKB Meta-analysis identified a novel genome-wide-significant locus for dental caries at rs4801882 in SIGLEC5 (P=1.71E-08); ungraded. Source: Table 2; Results 'Genome-wide association analysis of dental caries and periodontal disease'; Fig. 1a; Fig. 2b · same question in other reviews | Z-score (meta) -5.639 | 3 studies · 533348 participants | Ungraded |
ADGRL2 gene (aggregate gene-based signal, MAGMA) vs Genome-wide gene background (FDR threshold)
Population: Japanese adults (present-study direct-to-consumer genetic testing cohort); self-reported disease cases vs controls
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Dental caries (self-reported history) Lifelong (germline genotype) · MAGMA gene-based test (present study) Gene-based analysis found ADGRL2 significantly associated with dental caries (FDR q<0.05); ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease'; Tables S7-S8 · same question in other reviews | Gene-based association analysis (MAGMA): ADGRL2 was the only gene associated with dental caries at false-discovery-rate q<0.05 (no effect size reported). | 1 study · 45525 participants | Ungraded |
Genome-wide common variants (additive dosage; present-study GWAS) vs Genome-wide significance threshold (P<5E-8)
Population: Japanese adults (present-study cohort: 30,859 dental caries cases / 14,666 controls)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Dental caries - genome-wide-significant loci Lifelong (germline genotype) · Present-study GWAS (Japanese) The present Japanese GWAS found no genome-wide-significant loci for dental caries (top suggestive rs140784657); ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease'; Tables S3, S5 · same question in other reviews | In the present Japanese GWAS, no loci reached genome-wide significance (P<5E-8) for dental caries; several loci reached the suggestive level (P<1E-5). Top-associated variant rs140784657 (intergenic). All 47 lead… | 1 study · 45525 participants | Ungraded |
Dental caries - SNP-based heritability Lifelong (germline genotype) · LDSC heritability (present study) Population: Japanese adults (present-study cohort) SNP-based heritability of dental caries was low (h2=0.0258, SE 0.0155); ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease' · same question in other reviews | h2 (observed-scale SNP heritability) 0.0258 | 1 study · 45525 participants | Ungraded |
Genome-wide common variants (aggregate additive; LD score regression) vs Not applicable (variance-component estimate)
Population: Japanese adults (present-study cohort)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Periodontal disease - SNP-based heritability Lifelong (germline genotype) · LDSC heritability (present study) SNP-based heritability of periodontal disease was low (h2=0.0519, SE 0.0182); ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease' · same question in other reviews | h2 (observed-scale SNP heritability) 0.0519 | 1 study · 45525 participants | Ungraded |
Periodontal disease - genome-wide-significant loci (present study) Lifelong (germline genotype) · Present-study GWAS (Japanese) Population: Japanese adults (present-study cohort: 7,059 periodontal disease cases / 38,466 controls) The present Japanese GWAS found no genome-wide-significant loci for periodontal disease (top suggestive rs12624579/SYNDIG1); ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease'; Table S4 · same question in other reviews | In the present Japanese GWAS, no loci reached genome-wide significance for periodontal disease; several loci reached the suggestive level (P<1E-5). Top-associated variant rs12624579 (SYNDIG1 intron). | 1 study · 45525 participants | Ungraded |
Periodontal disease - novel loci (meta-analysis) Lifelong (germline genotype) · Meta-analysis: present study + GLIDE + UKB + BBJ Population: Adults from Japanese and European cohorts (present study + GLIDE + UK Biobank + BioBank Japan); periodontal disease cases vs controls The meta-analysis found no novel loci for periodontal disease; the European SIGLEC5/chr19 locus did not replicate in Japanese populations; ungraded. Source: Results 'Genome-wide association analysis of dental caries and periodontal disease'; Fig. 1b; Tables S6, S12 · same question in other reviews | Meta-analysis of periodontal disease identified only previously known loci; no novel loci. The chromosome-19 SIGLEC5 locus associated with periodontitis in Europeans was not replicated in Japanese populations (present… | 4 studies · 764572 participants | Ungraded |
Included primary studies 1
Open as a trial list| Study | Also included by | Outcomes it informs here | Trial PICO | Results |
|---|---|---|---|---|
| Shungin 2019 Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data. PMID:31235808 | 1 other review | not stated | not extracted yet | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match).
| Review | Shared studies | Jaccard |
|---|---|---|
| From teeth to bone: dental caries has causal effects on osteoporosis and osteoporotic fracture. (2025) | 1 | 0.33 |