title: Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.
abstract: Dental caries continues to be the most common chronic disease in children today. Despite the substantial involvement of genetics in the process of caries development, the specific genes contributing to dental caries remain largely unknown. We performed separate genome-wide association studies of smooth and pit-and-fissure tooth surface caries experience in the primary dentitions of self-reported white children in two samples from Iowa and rural Appalachia. In total, 1,006 children (ages 3-12 years) were included for smooth surface analysis, and 979 children (ages 4-14 years) for pit-and-fissure surface analysis. Associations were tested for more than 1.2 million single nucleotide polymorphisms, either genotyped or imputed. We detected genome-wide significant signals in KPNA4 (p value = 2.0E-9), and suggestive signals in ITGAL (p value = 2.1E-7) and PLUNC family genes (p value = 2.0E-6), thus nominating these novel loci as putative caries susceptibility genes. We also replicated associations observed in previous studies for MPPED2 (p value = 6.9E-6), AJAP1 (p value = 1.6E-6) and RPS6KA2 (p value = 7.3E-6). Replication of these associations in additional samples, as well as experimental studies to determine the biological functions of associated genetic variants, are warranted. Ultimately, efforts such as this may lead to a better understanding of caries etiology, and could eventually facilitate the development of new interventions and preventive measures.
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: E
authors.initials: E
authors.lastname: Feingold
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: D E
authors.initials: DE
authors.lastname: Weeks
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: D T
authors.initials: DT
authors.lastname: Cuenco
authors.forename: B
authors.initials: B
authors.lastname: Broffitt
authors.forename: R J
authors.initials: RJ
authors.lastname: Weyant
authors.forename: R
authors.initials: R
authors.lastname: Crout
authors.forename: D W
authors.initials: DW
authors.lastname: McNeil
authors.forename: S M
authors.initials: SM
authors.lastname: Levy
authors.forename: M L
authors.initials: ML
authors.lastname: Marazita
authors.forename: J R
authors.initials: JR
authors.lastname: Shaffer
mesh_terms: D000293:Adolescent; D001061:Appalachian Region; D040881:CD11a Antigen / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004245:DMF Index; D003731:Dental Caries / Q000235:genetics*; D003750:Dental Fissures / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007484:Iowa; D016350:Leucine Zippers / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics; D014094:Tooth, Deciduous / Q000473:pathology*; D028901:alpha Karyopherins / Q000235:genetics
chemical_list: C483313:AJAP1 protein, human; C485599:BPIFA1 protein, human; D040881:CD11a Antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; C106259:KPNA4 protein, human; D010750:Phosphoproteins; D028901:alpha Karyopherins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; C561977:MPPED2 protein, human; D010727:Phosphoric Diester Hydrolases