Uncovering the Genetic Architecture of NSCPO in Chinese via Subtype GWAS.

This article focuses on identifying genetic variants associated with nonsyndromic cleft palate only (NSCPO) in the Han Chinese population through subtype-specific genome-wide association studies (GWAS) and functional genomic analyses. The study found significant associations between NSCPO subtypes and single-nucleotide polymorphisms (SNPs) rs660975 in IRF6, rs3758244 in CDC37L1, and rs4880224 in BNIP3, with functional assays demonstrating that these variants affect enhancer activity and gene expression relevant to palate development. Notably, rs660975 exhibited an allele-specific effect, where the A allele increased risk for NSCPO and the C allele was associated with nonsyndromic cleft lip with or without palate (NSCL/P), suggesting a dosage-sensitive regulatory mechanism. The findings emphasize the importance of analyzing genetic contributions at the subtype level and within specific populations to better understand the complex etiology of cleft palate and to inform future clinical interventions.