Background: Genome-wide association studies (GWAS) have found more than 20 genes associated with a risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). However, the interactions between these risk genes have been rarely reported.
Methods: Here we selected 47 Single Nucleotide Polymorphisms (SNP) from previous GWASs and tested for possible interactions among 302 NSCL/P case-parent trios from a western Han Chinese population to further explore the genetic etiology of NSCL/P. Conditional logistic regression models were performed including gene-gene (G×G) interaction.
Results: Twenty pairwise interactions yielded significant p-values. Most of the signals of interaction between the SNPs were detected at the same gene including v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MAFB), netrin 1 (NTN1), and single nucleotide polymorphic marker within interferon regulatory factor 6 (IRF6). We found evidence of the interaction between rs17563 (bone morphogenetic protein 4, BMP4) and rs560426 (subfamily A member 4/Rho GTPase activating protein 29, ARHGAP29) (P=0.00093) in NSCLO trios.
Conclusions: Gene-gene interaction between markers in BMP4 and ARHGAP29 may influence the risk of NSCLO in western Han Chinese population, which might explain the missing heritability for NSCL/P.
Keywords: Case-parent trios; gene-gene interaction; non-syndromic cleft lip with or without cleft palate.
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