Association between single-nucleotide polymorphisms in endochondral development-related genes and 3D phenotypic variation of the cranial base

Background This study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in endochondral development-related genes and cranial base 3D phenotypes. Methods CBCT scans and the genomic DNA of 118 individuals were evaluated (age range: 15–66 years; 82 females). 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 BMP2 , BMP4 , RUNX2 , and SMAD6 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. Results 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 BMP2 rs1005464 as predictor variables, showed a strong explanatory power of the variation in the size of the cranial base (adjusted R 2 = 0.50). Individuals carrying at least one A allele for rs1005464 had larger cranial bases than common GG homozygotes (β = 0.015; 95% CI: 0.003, 0.027; P = 0.016). Fluctuating asymmetry scores were not associated with any of the evaluated SNPs. Conclusions The results suggest that BMP2 rs1005464 could be associated with variations in the cranial base size.