Novel Genetic Determinants of Dental Maturation in Children.
J Dent Res
; 102(3): 349-356, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36437532
ABSTRACT
Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3 P = 3.2 × 10-8), 14q13.3 (PAX9 P = 1.9 × 10-8), and 16q12.2 (IRX5 P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dente
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Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
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Systematic_reviews
Limite:
Animals
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Child
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Humans
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Infant
Idioma:
En
Revista:
J Dent Res
Ano de publicação:
2023
Tipo de documento:
Article