Lou Shu, Zhu Guirong, Xing Changyue, Hao Shushu, Lin Junyan, Xu Jiayi, Li Dandan, Du Yifei, Mi Congbo, Sun Lian, Wang Lin, Wang Meilin, Du Mulong, Pan Yongchu
State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University Nanjing China.
Department of Orthodontics, Affiliated Hospital of Stomatology Nanjing Medical University Nanjing China.
Imeta. 2024 Dec 20;3(6):e262. doi: 10.1002/imt2.262. eCollection 2024 Dec.
This study investigated pathogenic genes associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) through transcriptome-wide association studies (TWAS). By integrating expression quantitative trait loci (eQTL) data with genome-wide association study (GWAS) data, we identified key susceptibility genes, including . Notably, the variant rs12884809 G>A was associated with an increased risk of NSCL/P by enhancing the binding of the transcription factor ELK1 to the promoter, thereby activating its expression. This alteration in expression subsequently impacted mitophagy, leading to significant changes in cellular behavior and zebrafish morphology. Our findings illuminate the genetic mechanisms underlying NSCL/P and provide valuable insights for future prevention strategies and a deeper understanding of this condition.
本研究通过全转录组关联研究（TWAS）调查了与非综合征性唇裂伴或不伴腭裂（NSCL/P）相关的致病基因。通过将表达数量性状位点（eQTL）数据与全基因组关联研究（GWAS）数据相结合，我们确定了关键的易感基因，包括……。值得注意的是，变异体rs12884809 G>A通过增强转录因子ELK1与……启动子的结合，从而激活其表达，与NSCL/P风险增加相关。……表达的这种改变随后影响了线粒体自噬，导致细胞行为和斑马鱼形态发生显著变化。我们的研究结果阐明了NSCL/P的遗传机制，并为未来的预防策略和对这种疾病的更深入理解提供了有价值的见解。
