| Title: |
Novel Genetic Determinants of Dental Maturation in Children |
| Authors: |
Grgic, O.; Prijatelj, V.; Dudakovic, A.; Vucic, S.; Dhamo, B.; Trajanoska, K.; Monnereau, C.; Zrimsek, M.; Gautvik, K. M.; Reppe, S.; Shimizu, E.; Timpson, N. J.; Jaddoe, V. W.V.; Jarvelin, M. R.; Evans, D.; Uitterlinden, A. G.; Ongkosuwito, E. M.; van Wijnen, A. J.; Medina-Gomez, C.; Rivadeneira, F.; Wolvius, E. B. |
| Source: |
Grgic, O, Prijatelj, V, Dudakovic, A, Vucic, S, Dhamo, B, Trajanoska, K, Monnereau, C, Zrimsek, M, Gautvik, K M, Reppe, S, Shimizu, E, Timpson, N J, Jaddoe, V W V, Jarvelin, M R, Evans, D, Uitterlinden, A G, Ongkosuwito, E M, van Wijnen, A J, Medina-Gomez, C, Rivadeneira, F & Wolvius, E B 2023, 'Novel Genetic Determinants of Dental Maturation in Children', Journal of Dental Research, vol. 102, no. 3, pp. 349-356. https://doi.org/10.1177/00220345221132268 |
| Publication Year: |
2023 |
| Description: |
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, N 1 = 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 (N 2 = 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0022-0345; 1544-0591 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36437532; info:eu-repo/semantics/altIdentifier/wos/000891222700001; info:eu-repo/semantics/altIdentifier/pissn/0022-0345; info:eu-repo/semantics/altIdentifier/eissn/1544-0591 |
| DOI: |
10.1177/00220345221132268 |
| Availability: |
https://pure.eur.nl/en/publications/b52c06c8-3d38-491b-ac73-0f24e40ac4d5; https://doi.org/10.1177/00220345221132268; https://www.scopus.com/pages/publications/85148479282; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083589/pdf/10.1177_00220345221132268.pdf |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.52C07499 |
| Database: |
BASE |