Yiru Wang1, Jiayu Shi2, Qian Zheng1, Bing Shi1, Zhonglin Jia1. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University Chengdu, China. 2. Division of Growth, Development and Section of Orthodontics, School of Dentistry, University of California Los Angeles, USA.
Abstract
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. IJCEP
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. IJCEP
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