Genome-wide association study identifies four loci associated with eruption of permanent teeth

Frank Geller; Bjarke Feenstra; Hao Zhang; John R Shaffer; Thomas Hansen; Ann-Louise Esserlind; Heather A Boyd; Ellen A Nohr; Nicholas J Timpson; Ghazaleh Fatemifar; Lavinia Paternoster; David M Evans; Robert J Weyant; Steven M Levy; Mark Lathrop; George Davey Smith; Jeffrey C Murray; Jes Olesen; Thomas Werge; Mary L Marazita; Thorkild I A Sørensen; Mads Melbye

doi:10.1371/journal.pgen.1002275

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Genome-wide association study identifies four loci associated with eruption of permanent teeth

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Genome-wide association study identifies four loci associated with eruption of permanent teeth

Frank Geller, Bjarke Feenstra, Hao Zhang, John R Shaffer, Thomas Hansen, Ann-Louise Esserlind, Heather A Boyd, Ellen A Nohr, Nicholas J Timpson, Ghazaleh Fatemifar, …

PLoS genetics, Vol.7(9), e1002275

09/2011

DOI: 10.1371/journal.pgen.1002275

PMCID: PMC3169538

PMID: 21931568

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Abstract

The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P<5×10(-8) and were replicated in four independent study groups from the United States and Denmark with a total of 3,762 individuals; all combined P-values were below 10(-11). Two loci agreed with previous findings in primary tooth eruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9-4.1) fewer permanent teeth than children with 0 or 1 of these alleles.

Denmark

United States

Genome-Wide Association Study

Tooth, Deciduous - physiology

Membrane Proteins - genetics

Humans

Genotype

Male

Tooth Eruption - genetics

Peroxisomal Biogenesis Factor 2

Adolescent

Alleles

HMGA2 Protein - genetics

Polymorphism, Single Nucleotide - genetics

Female

Child

Cohort Studies

Details

Title: Subtitle: Genome-wide association study identifies four loci associated with eruption of permanent teeth
Creators: Frank Geller - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fge@ssi.dk
Bjarke Feenstra
Hao Zhang
John R Shaffer
Thomas Hansen
Ann-Louise Esserlind
Heather A Boyd
Ellen A Nohr
Nicholas J Timpson
Ghazaleh Fatemifar
Lavinia Paternoster
David M Evans
Robert J Weyant
Steven M Levy
Mark Lathrop
George Davey Smith
Jeffrey C Murray
Jes Olesen
Thomas Werge
Mary L Marazita
Thorkild I A Sørensen
Mads Melbye
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.7(9), e1002275
DOI: 10.1371/journal.pgen.1002275
PMID: 21931568
PMCID: PMC3169538
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: United States
Grant note: U01HG004423 / NHGRI NIH HHS\r\nU01 DE018903 / NIDCR NIH HHS\r\nR01 DE014899 / NIDCR NIH HHS\r\nWellcome Trust\r\nG0600705 / Medical Research Council\r\nR01 DE009551 / NIDCR NIH HHS\r\nU01HG004438 / NHGRI NIH HHS\r\nR01-DE12101 / NIDCR NIH HHS\r\nR01DE014899 / NIDCR NIH HHS\r\nWT 084762MA / Wellcome Trust\r\nU01HG004446 / NHGRI NIH HHS\r\nU01 HG004446 / NHGRI NIH HHS\r\nR01 DE012101 / NIDCR NIH HHS\r\nU01 HG004438 / NHGRI NIH HHS\r\nU01 HG004423 / NHGRI NIH HHS\r\nWT083431MA / Wellcome Trust\r\nHHSN268200782096C / NHGRI NIH HHS\r\nR01-DE 014899 / NIDCR NIH HHS\r\nR01DE012101 / NIDCR NIH HHS\r\nU01DE018903 / NIDCR NIH HHS\r\nHHSN268200782096C / NHLBI NIH HHS\r\nG0800582 / Medical Research Council\r\nR01-DE09551 / NIDCR NIH HHS\r\nR01DE009551 / NIDCR NIH HHS
Language: English
Date published: 09/2011
Academic Unit: Preventive and Community Dentistry; Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
Record Identifier: 9983917687402771

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