Genetic and Environmental Influences on Class II Malocclusion Phenotypes in a Yemeni Population: Insights from Cone‑Beam Computed Tomography Analysis

Background Class II malocclusion represents a prevalent orthodontic condition characterized by complex skeletal and dental discrepancies, influenced by both genetic predispositions and environmental factors. Phenotypic heterogeneity within this malocclusion hinders etiological investigations, particularly in underrepresented populations such as Yemenis. Objectives To characterize phenotypic variations in Class II malocclusion among Yemeni adults using cone‑beam computed tomography (CBCT), employing principal component analysis (PCA) and cluster analysis (CA) to identify distinct subgroups and explore potential genetic and environmental underpinnings. Methods A cross‑sectional sample of 120 Yemeni adults (aged 16–30 years; 53.3% female) with mild‑to‑severe Class II malocclusion was recruited from orthodontic clinics at Sana’a University and private practices. CBCT scans were acquired using standardized protocols (Vatech PaX‑Fle× 3D P2; 85–90 kV, 10 mA; 15×15 cm field of view; 0.3 mm voxel). Sixty‑three cephalometric measurements were derived from 30 landmarks. PCA reduced dimensionality and k‑means CA identified phenotypic clusters. Inter‑ and intra‑rater reliability was assessed via intraclass correlation coefficients (ICC > 0.85). Ethical approval was obtained from Sana’a University (Code 942), adhering to the Declaration of Helsinki. Results PCA yielded seven principal components explaining ~ 60% of variance, encompassing vertical dimensions, incisor angulation, mandibular length, maxillary position, facial taper, cranial base angulation, and maxillo‑mandibular relations. CA delineated five clusters: Cluster 1 (slightly retrusive maxilla and mandible); Cluster 2 (moderate mandibular retrusion with decreased mandibular plane angle); Cluster 3 (moderate maxillary prognathism with mandibular retrusion, short unit length, reduced posterior facial height); Cluster 4 (moderate maxillary protrusion, mandibular retrusion, steep mandibular plane, shortest ramus height); Cluster 5 (mild maxillary protrusion, mandibular retrusion, significantly reduced mandibular plane angle). Significant inter‑cluster differences were observed in skeletal and dental variables (ANOVA, p < 0.05). Conclusions Five distinct Class II phenotypes were identified in Yemeni adults, highlighting polygenic inheritance with environmental modulation. CBCT‑enhanced characterization reduces heterogeneity and provides a foundation for genome‑wide association studies and AI‑enabled orthodontic diagnostics in underrepresented populations.