GWAS Identified Loci Associated With Orthodontically EARR Of Maxillary Incisors

To identify the genetic susceptibility factors of orthodontic induced external apical root resorption (EARR) of maxillary incisors. The study was approved by the institutional ethics committee of the Affiliated Stomatological Hospital of NMU. Orthodontic patients were recruited. Root resorption volume was assessed from the three-dimensional structure of maxillary incisors of CBCT images using a pre-trained deep-learning model. The clinical variables, including gender, age, extraction pattern, and treatment duration, were evaluated. A genome-wide association study (GWAS) was performed to analyse the association between single-nucleotide polymorphisms (SNPs) and EARR severity by an additive model on the discovery and validation stages, respectively. Meta-analysis was adopted to combine the GWAS summary statistics of two stages, based on P value and weighted by sample size, magnitude and the direction of effect. Functional interpretation of the GWAS results were performed by FUMA. 167 and 211 orthodontic patients were recruited in two stages, respectively. Tooth structures were successfully reconstructed. No significant associations were found between EARR and gender, age, or extraction pattern. 7 susceptible loci (rs68057539, rs60614952, rs17159164, rs180716347, rs59586838, rs12232338, rs10880383) associated with EARR were identified in the meta-analysis. Enrichment of risk genes in acute inflammation response and immune effector processes pathways was revealed. 7 susceptibility loci associated with orthodontically induced EARR of maxillary incisors were identified in this GWAS, with subsequent functional enrichment analysis demonstrating significant overrepresentation of risk genes in inflammatory and immune-related pathways. These findings improved our understanding of the genetic factors underlying EARR.