Dataset Information

Gene-gene interactions between BMP4 and ARHGAP29 among non-syndromic cleft lip only (NSCLO) trios from western Han Chinese population.

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7061801 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gene-gene interactions between BMP4 and ARHGAP29 among non-syndromic cleft lip only (NSCLO) trios from western Han Chinese population.

Wang Yiru Y Shi Jiayu J Zheng Qian Q Shi Bing B Jia Zhonglin Z

International journal of clinical and experimental pathology 20200201 2

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32211112

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Project description:ObjectiveNon-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect, affecting 1.4 per 1 000 live births, and multiple genetic and environmental risk factors influencing its risk. All the known genetic risk factors accounted for a small proportion of the heritability. Several authors have suggested parent-of-origin effects (PoO) may play an important role in the etiology of this complex and heterogeneous malformation. To clarify the genetic association between PTCH1, PTCH2, SHH and SMO in hedgehog (HH) pathway and NSCL/P, as well as testing for potential PoO effects in Chinese case-parent trios.MethodsWe tested for transmission disequilibrium tests (TDT) and PoO effects using 83 common single nucleotide polymorphic (SNP) markers of HH pathway genes from 806 NSCL/P case-parent trios. These trios were drawn from an international consortium established for a genome-wide association studies (GWAS) of non-syndromic oral clefts of multiple ethnicities. DNA samples were collected from each trio. Single marker and haplotype based analysis were performed both in TDT tests and PoO effects. SNPs were excluded if they (ⅰ) had a call rate of < 95%, (ⅱ) had a minor allele frequency (MAF) of < 0.05, (ⅲ) had Mendelian errors over all trios of >5%, (ⅳ) had a genotype distribution in the parents that deviated from the Hardy-Weinberg equilibrium (HWE) (P < 0.000 1). The process was done using Plink (version 1.07, http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml). TDT test was performed in Plink v1.07. A log-linear model was used to explore PoO effects using Haplin v6.2.1 as implemented in R package v3.4.2. Significance level was assessed using the Bonferroni correction.ResultsA total of 18 SNPs were dropped due to low MAF, thus leaving 65 SNPs available for the analysis. Thus the Bonferroni threshold was 7.7×10-4 (0.05/65). Nominal significant association with NSCL/P was found at a SNP (rs4448343 in PTCH1, P=0.023) and six haplotypes (rs10512249-rs4448343, rs1461208-rs7786445, rs10512249-rs4448343, rs16909865-rs10512249-rs4448343, rs1461208-rs7786445-rs12698335, and rs288756-rs288758-rs1151790, P < 0.05). A total of six haplotypes (rs288765-rs1233563, rs12537550-rs11765352, rs872723-rs288765-rs1233563, rs288765-rs1233563-rs288756, rs6459952-rs12537550-rs11765352, and rs12537550-rs11765352-rs6971211) showed PoO effect (P < 0.05). None of the results remained significant after the Bonferroni correction (P>7.7×10-4).ConclusionNeither significant association between SNPs within HH pathway and the risk of NSCL/P nor PoO effects was seen in this study.

Dataset Information

Gene-gene interactions between BMP4 and ARHGAP29 among non-syndromic cleft lip only (NSCLO) trios from western Han Chinese population.

Publications

Gene-gene interactions between BMP4 and ARHGAP29 among non-syndromic cleft lip only (NSCLO) trios from western Han Chinese population.

Similar Datasets

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