Non-Cochrane · aetiology · PM36672800
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study.
Orlova Ekaterina, Dudding Tom, Chernus Jonathan M, et al. · Genes · 2022 · PubMed · doi:10.3390/genes14010059
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
16
current version
GRADE rated
0
No studies
0
Included studies
5
as reported
No studies 0 · 0%Ungraded 16 · 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 | Children under 6 years with vs without ECC (dmfs; AAPD definition); European / European non-Hispanic ancestry (population-stratification control) | 2974 children (ALSPAC n=1195, COHRA2 n=784, COHRA1 n=447, IFS n=391, IHS n=157); 843 ECC-affected, 2124 unaffected |
| Intervention | Genetic variation: common SNPs (MAF > 5%) genome-wide (GWAS) and genetically predicted gene expression (TWAS) | GWAS: 3,988,879 SNPs meta-analyzed (Stouffer's method); TWAS: genetically predicted expression across 49 GTEx v8 tissues (S-PrediXcan/S-MultiXcan) |
| Comparison | ECC-unaffected children (case-control genetic association) | ECC-unaffected children (n=2124) |
| Outcomes | Early childhood caries (ECC) | ECC: 0 genome-wide significant and 7 suggestive GWAS loci (p<1x10-5); TWAS identified 9 transcripts, of which 4 robust genes (CDH17, TAS2R43, SMIM10L1, TAS2R14) |
| Study designs | Five observational child cohorts with genome-wide genotyping, meta-analyzed | 5 cohort GWAS: COHRA1, COHRA2, Iowa Fluoride Study, Iowa Head Start, ALSPAC |
| Timing | Caries ascertained before age 6 (last available exam) | Cross-sectional (single caries assessment before age 6) |
Search date: Not applicable (no bibliographic literature search; primary meta-analysis of 5 pre-specified child cohorts). Databases: Not applicable - no literature database search. Genetic/phenotype data via dbGaP (phs001591.v1.p1, phs000095.v4.p2); GTEx v8 eQTL; 1000 Genomes and Haplotype Reference Consortium imputation panels
Questions and results
Common genetic variants genome-wide (GWAS; ~3.9 million SNPs with MAF > 5%) vs ECC-unaffected children (per-allele case-control association)
Population: Children up to age 5-6 years (European / European non-Hispanic ancestry); 843 ECC-affected vs 2124 unaffected across 5 cohorts (N=2974)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Early childhood caries (ECC) - association at lead SNP rs1044956 (7:24854765; nearest gene(s) OSBPL3, NPVF) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs1044956 (7:24854765); effect/non-effect allele A/G; MAF 0.49; direction across 5 cohorts +++++ The common variant rs1044956 near OSBPL3, NPVF showed suggestive (not genome-wide significant) association with ECC (Z = 4.551, p = 5.35e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) 4.551 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs563135 (10:115067899; nearest gene(s) TCF7L2, CASP7) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs563135 (10:115067899); effect/non-effect allele A/C; MAF 0.51; direction across 5 cohorts ----- The common variant rs563135 near TCF7L2, CASP7 showed suggestive (not genome-wide significant) association with ECC (Z = -4.532, p = 5.86e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) -4.532 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs7325099 (13:28104496; nearest gene(s) LNX2, POLR1D, RPL21) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs7325099 (13:28104496); effect/non-effect allele A/C; MAF 0.50; direction across 5 cohorts ++?++ The common variant rs7325099 near LNX2, POLR1D, RPL21 showed suggestive (not genome-wide significant) association with ECC (Z = 4.485, p = 7.28e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) 4.485 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs8091366 (18:24715618; nearest gene(s) CHST9, KCTD1) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs8091366 (18:24715618); effect/non-effect allele A/G; MAF 0.52; direction across 5 cohorts +++++ The common variant rs8091366 near CHST9, KCTD1 showed suggestive (not genome-wide significant) association with ECC (Z = 4.476, p = 7.60e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) 4.476 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs9889096 (16:13575143; nearest gene(s) SHISA9) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs9889096 (16:13575143); effect/non-effect allele T/G; MAF 0.50; direction across 5 cohorts --+-- The common variant rs9889096 near SHISA9 showed suggestive (not genome-wide significant) association with ECC (Z = -4.541, p = 5.59e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) -4.541 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs76823412 (8:134690570; nearest gene(s) ST3GAL1) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs76823412 (8:134690570); effect/non-effect allele T/C; MAF 0.47; direction across 5 cohorts +++++ The common variant rs76823412 near ST3GAL1 showed suggestive (not genome-wide significant) association with ECC (Z = 4.806, p = 1.54e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) 4.806 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association at lead SNP rs74470773 (3:33958083; nearest gene(s) PDCD6IP) Cross-sectional (ECC ascertained at the last dental exam before age 6) · rs74470773 (3:33958083); effect/non-effect allele T/C; MAF 0.47; direction across 5 cohorts ----- The common variant rs74470773 near PDCD6IP showed suggestive (not genome-wide significant) association with ECC (Z = -4.589, p = 4.46e-6); genetic association, ungraded. Source: Table 2; Results 3.1 (GWASs and GWAS Meta-Analysis); Figure 2 (Manhattan plot) · same question in other reviews | Z-score (Stouffer's combined Z, 5 cohorts) -4.589 | 5 studies · 2974 participants | Ungraded |
Genetically predicted gene expression (TWAS; S-PrediXcan with GTEx v8 cis-eQTL across 49 tissues; cross-tissue S-MultiXcan) vs ECC-unaffected children (association of genetically predicted expression)
Population: Children up to age 5-6 years (European / European non-Hispanic ancestry); 843 ECC-affected vs 2124 unaffected across 5 cohorts (N=2974)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Early childhood caries (ECC) - association with genetically predicted expression of SMIM10L1 (chr12p13.2) Cross-sectional (ECC ascertained at the last dental exam before age 6) · SMIM10L1 (chr12p13.2); 46 (3) tissues; significant (Bonferroni p < 3.09x10-6) Genetically predicted expression of SMIM10L1 was significantly associated with ECC in the TWAS (p = 1.70e-7); genetic association, ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) -0.35 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of TAS2R43 (chr12p13.2) Cross-sectional (ECC ascertained at the last dental exam before age 6) · TAS2R43 (chr12p13.2); 27 (3) tissues; significant (Bonferroni p < 3.09x10-6) Genetically predicted expression of TAS2R43 was significantly associated with ECC in the TWAS (p = 8.78e-8); genetic association, ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 1.80 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of LACC1 (chr13q14.11) Cross-sectional (ECC ascertained at the last dental exam before age 6) · LACC1 (chr13q14.11); 48 (4) tissues; suggestive (p < 1.0x10-4) ; flagged possible false positive Genetically predicted LACC1 expression reached the TWAS threshold for ECC (p = 3.98e-5) but was flagged as a possible false positive (LD misspecification) and not further considered; ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 0.10 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of NRAD1 (LINC00284) (chr13q14.11) Cross-sectional (ECC ascertained at the last dental exam before age 6) · NRAD1 (LINC00284) (chr13q14.11); 30 (5) tissues; significant (Bonferroni p < 3.09x10-6) ; flagged possible false positive Genetically predicted NRAD1 (LINC00284) expression reached the TWAS threshold for ECC (p = 1.69e-6) but was flagged as a possible false positive (LD misspecification) and not further considered; ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 0.13 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of TAS2R31 (chr12p13.2) Cross-sectional (ECC ascertained at the last dental exam before age 6) · TAS2R31 (chr12p13.2); 41 (4) tissues; suggestive (p < 1.0x10-4) Genetically predicted expression of TAS2R31 was suggestively associated with ECC in the TWAS (p = 1.04e-5); genetic association, ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) -0.25 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of TAS2R14 (chr12p13.2) Cross-sectional (ECC ascertained at the last dental exam before age 6) · TAS2R14 (chr12p13.2); 48 (4) tissues; significant (Bonferroni p < 3.09x10-6) Genetically predicted expression of TAS2R14 was significantly associated with ECC in the TWAS (p = 1.06e-6); genetic association, ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 0.47 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of IGSF5 (chr21q22.2) Cross-sectional (ECC ascertained at the last dental exam before age 6) · IGSF5 (chr21q22.2); 27 (11) tissues; suggestive (p < 1.0x10-4) ; flagged possible false positive Genetically predicted IGSF5 expression reached the TWAS threshold for ECC (p = 7.22e-5) but was flagged as a possible false positive (LD misspecification) and not further considered; ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 0.63 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of LINC02905 (C8orf49) (chr8p23.1) Cross-sectional (ECC ascertained at the last dental exam before age 6) · LINC02905 (C8orf49) (chr8p23.1); 9 (3) tissues; significant (Bonferroni p < 3.09x10-6) ; flagged possible false positive Genetically predicted LINC02905 (C8orf49) expression reached the TWAS threshold for ECC (p = 1.82e-8) but was flagged as a possible false positive (LD misspecification) and not further considered; ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) -0.35 | 5 studies · 2974 participants | Ungraded |
Early childhood caries (ECC) - association with genetically predicted expression of CDH17 (chr8q22.1) Cross-sectional (ECC ascertained at the last dental exam before age 6) · CDH17 (chr8q22.1); 23 (5) tissues; significant (Bonferroni p < 3.09x10-6) Genetically predicted expression of CDH17 was significantly associated with ECC in the TWAS (p = 3.32e-8); genetic association, ungraded. Source: Table 3; Results 3.2 (TWAS); Figure 3 (Manhattan plot) · same question in other reviews | Z-score (cross-tissue mean, S-MultiXcan) 1.74 | 5 studies · 2974 participants | Ungraded |