Targeted sequencing of NOTCH signaling pathway genes and association analysis of variants correlated with mandibular prognathism

INTRODUCTION: The purpose of this study was to systematically identify variants in NOTCH signaling pathway genes that correlate with mandibular prognathism (MP) in the general Chinese population. METHODS: Targeted sequencing of NOTCH signaling pathway genes was conducted in 199 MP individuals and 197 class I malocclusion control individuals. The associations of common and rare variants with MP, cephalometric parameters, and continuous cephalometric phenotypes were analyzed by principal component (PC) analysis. The associations between rare variants and MP were tested for each gene. RESULTS: Six SNPs, including rs415929, rs520688, and rs423023 in an exonic region of NOTCH4; rs1044006 in an exonic region of NOTCH3; rs1051415 in an exonic region of JAG1; and rs75236173 in the 3′-untranslated region (3′-UTR) of NUMB were associated with MP (P < 0.05). One common variant, rs1051415, in an exonic region of JAG1 was significantly related to PC1 (P = 3.608 × 10(− 4)), which explained 24.3% of the overall phenotypic variation observed and corresponded to the sagittal mandibular position towards the maxilla, ranging from a posterior positioned mandible to an anterior positioned mandible. Additionally, 41 other variants were associated with PC1–5 (P < 0.05). With respect to rare variant analysis, variants within the EP300, NCOR2, and PSEN2 gene showed an association with MP (t < 0 .05). CONCLUSIONS: An association between NOTCH signaling pathway genes and MP has been identified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13005-021-00268-0.