GWAS of dental caries patterns in the permanent dentition.
The importance of susceptibility genes in the risk for dental caries has been clearly established. While many candidate caries genes have been proposed, to date, few of them have been rigorously validated through observational and experimental studies. Moreover, most genetic epidemiological studies have analyzed global caries phenotypes that ignore the possibility that genes may exert differential effects across tooth surfaces of the dentition. Therefore, we performed genome-wide association studies (GWAS) of 5 novel dental caries phenotypes (developed by clustering the permanent dentition into categories of tooth surfaces based on co-occurrence of caries) to nominate new candidate caries genes. GWAS was performed in 920 self-reported white participants, aged 18 to 75 years, with genotype data on 518,997 genetic variants. We identified a significant genetic association between dental caries of the anterior mandibular teeth and LYZL2 (p value = 9e-9), which codes a bacteriolytic agent thought to be involved in host defense. We also identified a significant genetic association between caries of the mid- dentition tooth surfaces and AJAP1 (p value = 2e-8), a gene possibly involved in tooth development. Suggestive genetic associations were also observed for ABCG2, PKD2, the dentin/bone SCPP sub-family, EDNRA, TJFBR1, NKX2-3, IFT88, TWSG1, IL17D, and SMAD7 (p values < 7e-6). We nominate these novel genes for future study.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. jrs41@pitt.edu
J R
JR
Shaffer
E
E
Feingold
X
X
Wang
M
M
Lee
K
K
Tcuenco
D E
DE
Weeks
R J
RJ
Weyant
R
R
Crout
D W
DW
McNeil
M L
ML
Marazita
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001641:Bicuspid / Q000473:pathology; D015220:Calcium Channels / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D003481:Cuspid / Q000473:pathology; D004245:DMF Index; D003731:Dental Caries / Q000235:genetics*; D003733:Dental Caries Susceptibility / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007180:Incisor / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics; D008334:Mandible; D008875:Middle Aged; D009113:Muramidase / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D051906:Smad7 Protein / Q000235:genetics; D050396:TRPP Cation Channels / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; D020381:Interleukin-17; D009113:Muramidase; D009363:Neoplasm Proteins; D011506:Proteins; D051906:Smad7 Protein; D050396:TRPP Cation Channels; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C116614:ABCG2 protein, human; C483313:AJAP1 protein, human; C098623:IFT88 protein, human; C464462:IL17D protein, human; C534957:NKX2-3 protein, human; C497806:SMAD7 protein, human; C576635:TWSG1 protein, human; C507693:LYZL2 protein, human