Shared Genotypic Architectures of Stage III / IV Grade C Periodontitis Under 35 Years of Age (Former Aggressive Periodontitis) and Abnormal Root Morphology: A Family‐Based Study

Aim To identify shared genetic architectures and molecular pathways underlying the frequent co‐occurrence of stage III/IV grade C periodontitis under 35 years of age (PIII/IV‐C< 35y) and abnormal root morphology (ARM), using a family‐based SNP set and transcriptomic approach. Materials and Methods We conducted a family‐based study using whole‐genome genotyping of 148 Han Chinese individuals from 52 families, including 52 probands, 35 mothers, 32 fathers and 29 siblings. The participants included 65 comorbidity cases, 29 PIII/IV‐C< 35y‐only cases, 27 ARM‐only cases and 27 controls. Whole‐genome genotyping and bi‐clustering were used to identify SNP sets associated with each phenotype, and transcriptomic profiling was performed to validate gene expression changes. Results Among 109 SNP sets, 91 (83.5%) showed ≥ 40% comorbidity risk. Fifty‐four and 27 SNP sets were significantly associated with PIII/IV‐C< 35y and ARM, respectively. Six genotype subnetworks were enriched for neural development and inflammation pathways, particularly IL‐17 signalling. Transcriptome data confirmed down‐regulation of KLHL29 , HSF2 and COL13A1 in PIII/IV‐C< 35y, and a reduction in GJA1 expression in comorbidity cases. Conclusions This study reveals a shared genetic architecture between PIII/IV‐C< 35y and ARM, implicating neural development and inflammatory pathways in their co‐occurrence. Key genes such as GJA1 may advance mechanistic understanding and support early identification of high‐risk individuals.