Transcriptome-wide association identifies as a regulator of mitophagy in non-syndromic cleft lip with or without palate.

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.