Table 4 Suggestive loci observed for dft

12,125,935

2.78E-06

CD1D Gene product mediates mucosal immunity [90].

CD1A Encodes antigen-presenting protein expressed in oral epithelial cells [91].

CD1C Expressed in gingival environment on dendritic cells [92].

Locus contains clusters of OR6 and OR10 olfactory receptor family members [93].

PYHIN1 Involved in inflammasome activation in host response to pathogens [94]. Asthma susceptibility locus specific to African-American ancestry [95].

rs11718323

2.37E-06

1.06E-09

rs78777602

1.29E-06

4.67E-11

RARB Likely targeted by miRNAs involved in tooth morphogenesis and differentiation of dental cells [96]. Upregulated in ameloblastoma [53]. Has increased methylation in context of/is associated with head and neck squamous cell carcinoma, which is associated with dental hygiene and inflammation due to microbial factors [97].

rs1568206

9.33E-07

3.25E-08

rs1505809

4.99E-06

rs11932181

2.18E-06

rs1352733

3.47E-06

5.51E-08

rs62316615

2.68E-06

1.79E-10

GWAS signal is near gene desert that contains several enhancer elements that influence PITX2 expression involved in Axenfeld-Rieger syndrome, which presents with dental anomalies (hypodontia, delayed primary tooth eruption, retrognathia of maxilla and mandible) [98].

LARP7 Homozygous mutations cause Alazami syndrome, a feature of which is craniofacial dysmorphism [99].

MIR302A Promotes osteoblast differentiation [100].

rs57805404

1.54E-06

rs11741099

2.93E-06

4.22E-06

RUFY1 Encodes protein that is part of the machinery that addresses periodontal pathogen intrusions in oral epithelial barriers [101].

MAML1 Part of Notch signaling pathway, plays role in bone development [102].

GRM6 Transcribed in a healthy gingival state [103].

GWAS signal is intronic variant to ADAMTS2; homozygous mutations cause Ehlers-Danlos syndrome type VIIC, features of which include multiple tooth agenesis and dentin defects [104]. ADAMTS proteins are believed to play a role in various airway pathologies, including asthma [105].

rs61497549

2.78E-06

MIR6874 Upregulated in periodontal ligament cells when exposed to LPS of P. gingivalis [106].

rs1235058

3.14E-06

1.53E-05

HPVC1 Candidate gene for a complex chronic periodontitis trait involving a mixed infection bacterial community [107].

VSTM2A Exhibits high expression in mandibular molars relative to incisors [108].

EGFR EGF-receptors are found on the dental follicle, alceolar bone, and ameloblasts before and during tooth eruption [109, 110]. EGFR is a biomarker for neoplastic potential of dysplastic oral tissues [111]. Product mediates proliferation of gingival fibroblasts [112].

rs2515501

4.54E-06

4.39E-10

ANGPT2 Upregulated in response to P. gingivalis; elevated levels are associated with oral squamous cell carcinoma [113]).

DEFB1 Encodes anti-microbial peptide; polymorphisms in DEFB1 are associated with > 5 fold increase in DMFT/DMFS scores [114] and general DMFT index [115].

DEFB1, −A1, −A1B, −A1P, −A3, −A4, −A6, −A8P, −9P, −A10, −T1P2 The defensin family (DEF-) of antimicrobial peptides (Ganz 2003), is involved in chronic periodontal inflammation [116], and oral carcinogenesis [117].

rs10504504

3.23E-06

4.98E-09

rs74949229

4.38E-06

2.53E-09

rs6585998

2.78E-06

1.79E-05

MIR346 Involved in osteogenic differentiation of human bone marrow mesenchymal stem cells [118].

rs11020123

4.10E-06

4.16E-07

FAT3 One of genes enriched in the GO category “calcium ion binding” that are differentially expressed throughout different stages of tooth development [119].

MTNR1B Locus associated with type II diabetes [120].

rs79812076

2.17E-06

3.16E-08

IGF1 Encodes metabolism regulator of hard dental tissue through action on IGF1-receptor; is involved in later stages of tooth development and pulpal differentiation [121].

rs9630337

4.47E-06

3.07E-11

chr13:96271864

3.62E-06

CLDN10 Expressed in preodontoblasts, and restricted to the lingual basal epithelium of the tooth bud [122].

HS6ST3 Associated with obesity (BMI ≥ 35 kg/m2) [123].

rs422342

2.39E-06

1.20E-05

SMAD6 Highly expressed in bone, including mandible and palatal bone [124].

SMAD3 Expressed in intramembranous bones and submandibular salivary gland [124].

MAP 2 K5 Associated with BMI [125].

rs7174369

1.72E-06

1.68E-06

MEF2A Regulates osteogenic differentiation of dental pulp stem cells [126].

IGF1R IGF-receptor; involved in signaling in dental fibroblast apoptosis [127].

rs9915753

4.50E-06

1.81E-07

SLC9A3R1 Mutations cause hypophosphatemic nephrolithiasis/osteoporosis 2, features of which can include skeletal defects, fractures, and osteoporosis/osteopenia [128].

rs2012033

8.21E-07

5.37E-06

CHST8 Candidate gene for hypodontia [129].

KCTD15 Associated with obesity and preference for carbohydrates [130].

rs55928325

4.70E-06

6.11E-07

NLRP5 Increased expression in mucosa in state of periodontitis [131], and part of gene expression network preferentially expressed in lower incisors [108].

ZNF582 Hypermethylation is associated with oral dysplasia and cancer [132].