Transcriptome‐wide association identifies KLC1 as a regulator of mitophagy in non‐syndromic cleft lip with or without palate

作者：Shu Lou, Guirong Zhu, Changyue Xing, Shushu Hao, Junyan Lin, Jiayi Xu, Dandan Li, Yifei Du, Congbo Mi, Lian Sun, Lin Wang, Meilin Wang, Mulong Du, Yongchu Pan · 发表于：iMeta · 年份：2024 · DOI：10.1002/imt2.262 · 被引用次数：4 · 研究领域：Cleft Lip and Palate Research、Head and Neck Cancer Studies、Craniofacial Disorders and Treatments

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 KLC1. 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 KLC1 promoter, thereby activating its expression. This alteration in KLC1 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.