title: Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.
abstract: While genetics clearly influences dental caries risk, few caries genes have been discovered and validated. Recent studies have suggested differential genetic factors for primary dentition caries and permanent dentition caries, as well as for pit-and-fissure- (PF) and smooth- (SM) surface caries. We performed separate GWAS for caries in permanent-dentition PF surfaces (1,017 participants, adjusted for age, sex, and the presence of Streptococcus mutans) and SM surfaces (1,004 participants, adjusted for age, education group, and the presence of Streptococcus mutans) in self-reported whites (ages 14 to 56 yrs). Caries scores were derived based on visual assessment of each surface of each tooth; more than 1.2 million SNPs were either successfully genotyped or imputed and were tested for association. Two homologous genes were suggestively associated: BCOR (Xp11.4) in PF-surface caries (p value = 1.8E-7), and BCORL1 (Xq26.1) in SM-surface caries (p value = 1.0E-5). BCOR mutations cause oculofaciocardiodental syndrome, a Mendelian disease involving multiple dental anomalies. Associations of other plausible cariogenesis genes were also observed for PF-surface caries (e.g., INHBA, p value = 6.5E-6) and for SM-surface caries (e.g., CXCR1 and CXCR2, p value = 1.9E-6). This study supports the notion that genes differentially affect cariogenesis across the surfaces of the permanent dentition, and nominates several novel genes for investigation.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: J R
authors.initials: JR
authors.lastname: Shaffer
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Feingold
authors.forename: D E
authors.initials: DE
authors.lastname: Weeks
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: K T
authors.initials: KT
authors.lastname: Cuenco
authors.forename: S K
authors.initials: SK
authors.lastname: Wendell
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: M L
authors.initials: ML
authors.lastname: Marazita
mesh_terms: D000293:Adolescent; D000328:Adult; D003731:Dental Caries / Q000145:classification / Q000235:genetics*; D003733:Dental Caries Susceptibility / Q000235:genetics*; D019229:Dentition, Permanent; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D028322:Inhibin-beta Subunits / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D023062:Receptors, Interleukin-8A / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012737:Sex Factors; D055815:Young Adult
chemical_list: C411984:BCOR protein, human; C521111:BCORL1 protein, human; D011518:Proto-Oncogene Proteins; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D012097:Repressor Proteins; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits