Table 2 Suggestive loci observed for DMFT
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 | GWAS P-value | Effect Size | SE | |||||
rs74086974 | 1 | 71,335,753 | 4.522 | 0.904 | 3.18E-06 | Â | Â | Â | PTGER3 Candidate gene for role in outcome of periodontal therapy and preterm birth [38]. ZRANB2 Affects bone morphogenic signaling [39]. Protein product binds bacterial LPS and Gram-negative bacteria, and has antibacterial function [40]. MIR186 Expressed differentially in health gingiva versus periodontitis gingiva [41]. |
rs1003652 | 2 | 10,468,296 | −3.563 | 0.734 | 4.39E-06 | 0.09572 | 0.4685 | 2.66E-05 | TAF1B Associated with non-syndromic cleft lip with palate in Chinese [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]. |
rs340349 | 2 | 179,933,412 | 4.79 | 0.833 | 2.20E-07 | 1.069 | 0.544 | 0.000184 | Â |
rs6434873 | 2 | 197,504,826 | 3.955 | 0.818 | 4.19E-06 | −0.02973 | 0.3442 | 7.11E-06 | PGAP1 Mouse gene knockout results in severe facial abnormalities, including lack of mouth, tongue, and mandible [47]. |
rs12488352 | 3 | 14,725,668 | 3.736 | 0.764 | 3.20E-06 | −0.9612 | 0.526 | 4.07E-07 |  |
rs6441084 | 3 | 156,310,776 | 4.57 | 0.904 | 3.26E-06 | Â | Â | Â | Â |
chr3:194035416 | 3 | 194,035,416 | −5.782 | 0.891 | 1.60E-07 |  |  |  | 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]. |
rs62295581 | 4 | 11,844,859 | 6.403 | 1.173 | 2.05E-06 | −0.6366 | 0.5008 | 3.40E-08 |  |
chr4:158617368 | 4 | 158,617,368 | 7.46 | 1.375 | 2.76E-06 | Â | Â | Â | Â |
rs28503910 | 4 | 182,680,709 | 4.983 | 0.973 | 4.84E-06 | 0.1327 | 0.4536 | 6.27E-06 | MIR1305 Upregulated in smoker periodontal ligament-derived stem cells, and may impair the regenerative potential of this tissue [52]. |
rs12171500 | 5 | 76,460,134 | 15.92 | 2.507 | 1.37E-06 | 0.1616 | 0.4686 | 6.46E-10 | IQGAP2 Involved in tooth development; upregulated in ameloblastoma [53]. S100Z 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]. |
rs12154393 | 7 | 11,210,931 | 3.828 | 0.762 | 3.06E-06 | 0.1274 | 0.3092 | 6.86E-06 | NDUFA4 Candidate gene for role in cellular aging in dental follicle stem cells [57]. THSD7A Obesity candidate gene [58]. |
rs6947348 | 7 | 26,383,748 | 4.615 | 0.799 | 1.70E-07 | 0.3809 | 0.437 | 3.35E-06 | MIR148 Involved in dental stem cells [59]. SNX10 Mutations cause malignant osteopetrosis of infancy [60], a disease of increased bone mass that also has dental manifestations of delayed tooth eruption, congenitally missing or malformed teeth, and osteomyelitis and osteonecrosis of the jaw [61]. |
rs10224789 | 7 | 111,953,442 | 5.797 | 1.041 | 8.19E-07 | Â | Â | Â | IFRD1 Nociceptive pathway gene and risk factor for temporomandibular disorders [62]. |
rs817156 | 9 | 98,469,359 | 4.865 | 0.982 | 3.99E-06 | −0.2586 | 0.3784 | 1.13E-06 | PTCH1 Encodes the main receptor for the Hedgehog signaling pathway; mutations can cause odontogenic keratocysts, orofacial clefting, and hypodontia [63]. |
rs112246048 | 10 | 7,562,045 | 4.998 | 0.948 | 3.89E-06 | −0.7608 | 0.6298 | 4.20E-07 |  |
rs7107282 | 11 | 26,965,751 | 3.959 | 0.805 | 3.21E-06 | Â | Â | Â | SLC5A12 Lactate transporter in T-cells which enables T-cells to sense inflammatory environments [64]. CCDC34 Bone mineral density-related candidate gene [65]. LGR4 Required for sequential development of molars [66]. |
rs483743 | 13 | 113,786,947 | 3.82 | 0.743 | 1.39E-06 | −0.08544 | 0.4209 | 4.82E-06 |  |
rs4331298 | 15 | 71,918,351 | 4.054 | 0.818 | 3.01E-06 | −0.6631 | 0.3067 | 6.75E-08 |  |
rs72787939 | 16 | 26,556,887 | 4.617 | 0.819 | 6.34E-07 | −1.076 | 0.4973 | 2.81E-09 |  |
chr16:28719857 | 16 | 28,719,857 | 5.25 | 0.962 | 4.36E-06 | Â | Â | Â | APOBR Associated with body fat percentage [67] (Lu et al., 2016). SH2B1 Associated with BMI, and is implicated in leptin signaling [68]. |
rs2317828 | 16 | 82,266,591 | 3.72 | 0.727 | 1.55E-06 | Â | Â | Â | PLCG2 May play crucial role in odontogenesis [69]. CDH13 Gene product may regulate the morphogenesis and rearrangement of secretory ameloblast cells [70]. |
rs321946 | 19 | 52,859,828 | −3.552 | 0.716 | 2.54E-06 | 0.5165 | 0.4073 | 7.83E-07 |  |
rs62225548 | 21 | 41,902,731 | −3.693 | 0.700 | 6.41E-07 | −0.2548 | 0.3871 | 1.71E-05 |  |
rs2838538 | 21 | 45,687,271 | 4.606 | 0.914 | 4.34E-06 | −0.1598 | 0.3027 | 7.48E-07 | CTSB Salivary levels of encoded protein are reduced in chronic graft-versus-host disease, which affects the saliva in the majority of patients [71]. AIRE Mutations cause autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy, a feature of which can be dental abnormalities [72]. TRPM2 Encodes an ion channel whose expression is increased in dental pulpitis. TRPM2 is activated in cancer radiation treatments to suppress Ca2+ signaling required for saliva production [73]. TSPEAR Mutations affect Notch signaling and cause an ectodermal dysplasia causing features including hypodontia [74]. |