Novel Genetic Determinants of Dental Maturation in Children
| Autor: | O. Grgic, V. Prijatelj, A. Dudakovic, S. Vucic, B. Dhamo, K. Trajanoska, C. Monnereau, M. Zrimsek, K.M. Gautvik, S. Reppe, E. Shimizu, S. Haworth, N.J. Timpson, V.W.V. Jaddoe, M.-R. Jarvelin, D. Evans, A.G. Uitterlinden, E.M. Ongkosuwito, A.J. van Wijnen, C. Medina-Gomez, F. Rivadeneira, E.B. Wolvius |
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| Přispěvatelé: | Oral and Maxillofacial Surgery, Pediatrics, Internal Medicine |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal of Dental Research, 102(3), 349-356. SAGE Publishing Journal of Dental Research, 102, 3, pp. 349-356 Journal of Dental Research, 102, 349-356 |
| ISSN: | 0022-0345 |
| DOI: | 10.1177/00220345221132268 |
| Popis: | 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 −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. |
| Databáze: | OpenAIRE |
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