Objectives: To study the association between the seven cell-cell adherens junctions (AJs) -related genes (CDH1, CTNND1, CTNNA1, ESRP1, ESRP2, PLEKHA5, and PLEKHA7) and non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Asian population.
Design: The study included 895 NSCL/P case-parent trios of Asian ethnicity drawn from an international consortium established for a genome-wide association study. We performed association analysis by applying the genotypic transmission disequilibrium test for each of the 144 single nucleotide polymorphisms (SNPs), the versatile gene-based association study for the combined effects of all SNPs, all in or around the seven target genes, and the versatile pathway-based approach for the combined effects of these seven target genes, consecutively.
Results: In our analysis, we found neither a significant SNP-based nor gene-based association with NSCL/P for any of the 144 relevant SNPs or the seven target genes. However, novel evidence of a significant association (P = 6.00 × 10-6) with NSCL/P was observed in the combined effects of these seven target genes in the versatile pathway-based analysis.
Conclusions: Our results were consistent with the findings of previously published human sequencing studies and reinforced the role of these cell-cell AJs-related genes in the pathogenesis of NSCL/P that may be replicated using data from other genome-wide association studies. This pathway approach better reflects our current understanding of the biological mechanisms underlying the aetiology of NSCL/P.
Keywords: Adherens junctions; Cleft lip; Cleft palate; Genetic association studies; Single nucleotide polymorphism.
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