Targeted sequencing in FGF/FGFR genes and association analysis of variants for mandibular prognathism

To identify variants of the genes in fibroblast growth factors/fibroblast growth factor receptors (FGF/FGFR) signal pathway that predispose to mandibular prognathism (MP) in the general Chinese population systematically. Targeted sequencing of the FGF/FGFR genes was conducted in 176 MP individuals and 155 class I malocclusion controls. The associations of common and rare variants with MP as a categorical phenotype and also continuous malocclusion phenotypes generated by principal component (PC) analysis were analyzed. One common variant, rs372127537, located in the 3’-untranslated region of FGF7 gene, was significantly related to PC1 (P = 4.22 × 10(–4)), which explained 23.23% of the overall phenotypic variation observed and corresponded to vertical discrepancies ranging from short anterior face height to long anterior face height, after Bonferroni correction. Also, 15 other variants were associated with PC1–4, although not significant after multiple corrections (P < .05). We also identified 3 variants: rs13317 in FGFR1, rs149242678 in FGF20, and rs79176051 FGF12 associated with MP (P < .05). With respect to rare variant analysis, variants within the FGF12 gene showed significant association with MP (P = .001). Association between FGF/FGFR signaling pathway and MP has been identified. We found a previously unreported SNP in FGF7 significantly related to increased facial height. Also, rare variants within the FGF12 were associated with MP. Our results provide new clues for genetic mechanisms of MP and shed light on strategies for evaluating rare variants that underlie complex traits. Future studies with larger sample sizes and more comprehensive genome coverage, and also in other population are required to replicate these findings.