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Data from eleven 3D landmarks identified at the cranial base were subjected to geometric morphometric analysis, including Procrustes fit, principal component (PC) analyses, and estimation of centroid sizes and fluctuating asymmetry scores. Seven SNPs within\n                      <jats:italic>BMP2<\/jats:italic>\n                      ,\n                      <jats:italic>BMP4<\/jats:italic>\n                      ,\n                      <jats:italic>RUNX2<\/jats:italic>\n                      , and\n                      <jats:italic>SMAD6<\/jats:italic>\n                      were genotyped by real-time PCR. General linear models (GLM) were fitted to assess the effect of SNPs on cranial base shape, size, and symmetry quantitative traits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven PCs were identified for each shape variation aspect (i.e., symmetric and asymmetric components). These explained 81.9% and 84.6% of the total variation, respectively. GLM did not evidence strong associations between cranial base shape aspects and the studied SNPs. GLM including age, sex and\n                      <jats:italic>BMP2<\/jats:italic>\n                      rs1005464 as predictor variables, showed a strong explanatory power of the variation in the size of the cranial base (adjusted R\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.50). Individuals carrying at least one A allele for rs1005464 had larger cranial bases than common GG homozygotes (\u03b2\u2009=\u20090.015; 95% CI: 0.003, 0.027;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.016). Fluctuating asymmetry scores were not associated with any of the evaluated SNPs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The results suggest that\n                      <jats:italic>BMP2<\/jats:italic>\n                      rs1005464 could be associated with variations in the cranial base size.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13005-026-00644-8","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:48:17Z","timestamp":1784645297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between single-nucleotide polymorphisms in endochondral development-related genes and 3D phenotypic variation of the cranial base"],"prefix":"10.1186","volume":"22","author":[{"given":"Guido Artemio","family":"Mara\u00f1\u00f3n-V\u00e1squez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica","family":"Tirre de Souza Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio","family":"Carlos de Oliveira Ruellas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00edrian Aiko Nakane","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro David Avalos","family":"Ch\u00e1vez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcio","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds","family":"de Oliveira Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia Azeredo Alves","family":"Antunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Lagrav\u00e8re Vich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Scariot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Flores-Mir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kirschneck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"dos Santos Antunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Calvano","family":"K\u00fcchler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"644_CR1","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1111\/j.1469-7580.2011.01346.x","volume":"218","author":"N Gkantidis","year":"2011","unstructured":"Gkantidis N, Halazonetis DJ. 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Burlington: Academic; 2004."}],"container-title":["Head &amp; Face Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13005-026-00644-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13005-026-00644-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13005-026-00644-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:01:50Z","timestamp":1784872910000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13005-026-00644-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["644"],"URL":"https:\/\/doi.org\/10.1186\/s13005-026-00644-8","relation":{},"ISSN":["1746-160X"],"issn-type":[{"value":"1746-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"29 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Research Ethics Committee of the School of Dentistry of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, approved the protocol of this study (n. 3.150.551). Signed written informed consent was obtained from all participants and \/ or legal guardians at the beginning of the study.","order":1,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"62"}}