Table 3 Suggestive loci observed for DMFS
From: Pilot GWAS of caries in African-Americans shows genetic heterogeneity
Lead SNP | CHR | BP | African-American cohort | Caucasian cohort | Q Statistic P-value | Nearby Gene(s) and Corroborating Evidence | |||
|---|---|---|---|---|---|---|---|---|---|
Effect Size | SE | P-value | Effect Size | SE | |||||
rs1122613 | 1 | 3,768,565 | −12.54 | 2.525 | 2.72E-06 | 1.395 | 1.121 | 4.56E-07 | ARHGEF16 Candidate biomarker for diagnosis of oral squamous cell carcinoma [75]. |
rs1003652 | 2 | 10,468,296 | −11.67 | 2.47 | 4.54E-06 | 1.04 | 1.497 | 9.86E-06 | TAF1B Candidate gene for susceptibility to non-syndromic cleft lip with palate [42]. GRHL1 Differentially expressed between gingiva and dental follicles [43], differentially regulated in primary pulp stem cells by enamel matrix derivative [44]. KLF11 Involved in tooth development, specifically odontoblast differentiation [45]. PDIA6 Differentially expressed in soft tissue and bone after tooth extraction [46]. |
rs12488352 | 3 | 14,725,668 | 12.68 | 2.576 | 2.97E-06 | − 3.552 | 1.679 | 1.30E-07 |  |
chr3:194035416 | 3 | 194,035,416 | −18.1 | 3.34 | 2.48E-06 |  |  |  | HES1 Part of Notch signaling pathway involved in tooth development [48]. Promotes antimicrobial response in epithelial cells [49]. Regulates taste cell differentiation, specifically of the sweet-, bitter-, and umami-sensing cells [50]. LSG1 Differentially expressed between the sexes in minor salivary glands [51]. |
rs28503910 | 4 | 182,680,709 | 17.13 | 3.055 | 1.99E-06 | −0.9102 | 1.454 | 9.71E-08 |  |
rs12171500 | 5 | 76,460,134 | 57.37 | 7.984 | 1.96E-06 | 0.8305 | 1.491 | 3.37E-12 | IQGAP2 Involved in tooth development; upregulated in ameloblastoma [53]. S100Z Upregulated as part of ameloblastoma signature [54]. SNORA47 Upregulated as part of ameloblastoma signature [54]. CRHBP One of most up-regulated genes in deciduous tooth pulp, as compared to that of permanent teeth [55]. F2R Encodes a transcription factor (PAR1) important for enamel formation [56]. |
rs6947348 | 7 | 26,383,748 | 14.59 | 2.698 | 1.38E-06 | 1.265 | 1.402 | 1.17E-05 | MIR148 Involved in dental stem cells [59]. |
rs66691214 | 7 | 30,188,804 | 13.79 | 2.459 | 7.24E-07 | 0.9477 | 0.9689 | 1.18E-06 | FKBP14 Mutations cause Ehlers-Danlos Syndrome [76], which can have oral manifestations [77]. NOD1 Innate immunity gene expressed by dental pulp fibroblasts in the recognition of invaded caries-related bacteria and the subsequent innate immune responses [78]; gene product mediates sensing of periodontal pathogens [79], including P. gingivalis [80]. Required for the bone resorption consequences of immune activation by commensal bacteria in a model of periodontitis [81]. |
rs7011390 | 8 | 66,304,329 | 12.96 | 2.634 | 3.48E-06 | 0.7342 | 1.329 | 3.41E-05 | Â |
rs72787939 | 16 | 26,556,887 | 15.85 | 2.63 | 2.20E-07 | −4.171 | 1.594 | 7.51E-11 | HS3ST4 Heparan sulfate proteoglycans are coreceptors for FGFR22b, whose signaling is essential for progenitor survival and proliferation in several organs, including the submandibular gland and the tooth [82] |
rs4801855 | 19 | 51,348,572 | − 17.33 | 3.459 | 3.24E-06 | − 0.4175 | 1.005 | 2.66E-06 | POLD1 Mutations cause Mandibular Hypoplasia, Deafness and Progeroid features (MDP) syndrome, a premature aging syndrome which results in severe dental crowding and irregular teeth [83]. ACPT Recessive mutations in ACPT cause hypoplastic amelogenesis imperfecta; ACPT supplies phosphate during dentine formation [84]. KLK1 Protein product is abundant in salivary proteome [85], and is involved in cellular inflammatory processes [86]. KLK4 Homozygous mutations cause hypomaturation amelogenesis imperfecta [87]. SIGLEC9 Modulates innate immunity [88]. CD33 Encodes immunomodulatory receptor [89]. |