{"doi":"10.1177/00220345221132268","title":"Novel Genetic Determinants of Dental Maturation in Children","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, 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.","journal":"Journal of Dental Research","year":2022,"id":277291,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9335,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":948365,"name":"Vid Prijatelj","orcid":"0000-0002-9463-3962","position":1,"is_corresponding":false},{"id":275539,"name":"Amel Dudakovic","orcid":"0000-0002-8850-3977","position":2,"is_corresponding":false},{"id":948366,"name":"S. Vucic","orcid":"0000-0003-3352-3900","position":3,"is_corresponding":false},{"id":948367,"name":"Brunilda Dhamo","orcid":"0000-0002-5537-067X","position":4,"is_corresponding":false},{"id":271810,"name":"Katerina Trajanoska","orcid":"0000-0002-3792-4296","position":5,"is_corresponding":false},{"id":241458,"name":"Claire Monnereau","orcid":"0000-0002-1768-7705","position":6,"is_corresponding":false},{"id":948368,"name":"Maša Zrimšek","orcid":"0000-0003-4950-1386","position":7,"is_corresponding":false},{"id":948369,"name":"Kaare M. Gautvik","orcid":"0000-0002-9023-6513","position":8,"is_corresponding":false},{"id":948370,"name":"Sjur Reppe","orcid":"0000-0002-4330-5379","position":9,"is_corresponding":false},{"id":644198,"name":"Emi Shimizu","orcid":"0000-0002-1209-2286","position":10,"is_corresponding":false},{"id":560480,"name":"Simon Haworth","orcid":"0000-0001-7793-7326","position":11,"is_corresponding":false},{"id":42602,"name":"Nicholas J. Timpson","orcid":"0000-0002-7141-9189","position":12,"is_corresponding":false},{"id":279629,"name":"Vincent W. V. Jaddoe","orcid":"0000-0003-2939-0041","position":13,"is_corresponding":false},{"id":22043,"name":"Marjo‐Riitta Järvelin","orcid":"0000-0002-2149-0630","position":14,"is_corresponding":false},{"id":228683,"name":"David M. Evans","orcid":"0000-0003-0663-4621","position":15,"is_corresponding":false},{"id":5303,"name":"André G. Uitterlinden","orcid":"0000-0002-7276-3387","position":16,"is_corresponding":false},{"id":948371,"name":"Edwin M. Ongkosuwito","orcid":"0000-0001-9250-027X","position":17,"is_corresponding":false},{"id":275536,"name":"André J. van Wijnen","orcid":"0000-0002-4458-0946","position":18,"is_corresponding":false},{"id":22016,"name":"Carolina Medina‐Gómez","orcid":"0000-0001-7999-5538","position":19,"is_corresponding":false},{"id":16431,"name":"Fernando Rivadeneira","orcid":"0000-0001-9435-9441","position":20,"is_corresponding":false},{"id":948372,"name":"Eppo B. 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