title: Genome-wide association scan for childhood caries implicates novel genes.
abstract: Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
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: M
authors.initials: M
authors.lastname: Lee
authors.forename: F
authors.initials: F
authors.lastname: Begum
authors.forename: D E
authors.initials: DE
authors.lastname: Weeks
authors.forename: K T
authors.initials: KT
authors.lastname: Cuenco
authors.forename: M M
authors.initials: MM
authors.lastname: Barmada
authors.forename: S K
authors.initials: SK
authors.lastname: Wendell
authors.forename: D R
authors.initials: DR
authors.lastname: Crosslin
authors.forename: C C
authors.initials: CC
authors.lastname: Laurie
authors.forename: K F
authors.initials: KF
authors.lastname: Doheny
authors.forename: E W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Feenstra
authors.forename: F
authors.initials: F
authors.lastname: Geller
authors.forename: H A
authors.initials: HA
authors.lastname: Boyd
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Melbye
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
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: R L
authors.initials: RL
authors.lastname: Slayton
authors.forename: M C
authors.initials: MC
authors.lastname: Willing
authors.forename: B
authors.initials: B
authors.lastname: Broffitt
authors.forename: A R
authors.initials: AR
authors.lastname: Vieira
authors.forename: M L
authors.initials: ML
authors.lastname: Marazita
mesh_terms: D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D003731:Dental Caries / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014481:United States