Wang M Y, Li W Y, Zhou R, Wang S Y, Liu D J, Zheng H C, Li J, Li N, Zhou Z B, Zhu H P, Wu T, Hu Y H
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Oct 18;52(5):815-820. doi: 10.19723/j.issn.1671-167X.2020.05.004.
In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction.
We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10 using Bonferroni correction.
A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction ( < 3.47×10) after Bonferroni correction, which were rs7618735 () and rs10848543 (), rs631948 () and rs556874 (), and rs631948 () and rs472631 () among NSCL/P trios; rs589149 () and rs4765834 (), rs1402704 () and rs358792 (), and rs1402704 () and rs358793 () among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios.
Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.
在本研究中，我们使用全基因组关联研究（GWAS）数据，考虑基因-基因相互作用和基因-环境相互作用，探讨WNT信号通路基因是否与非综合征性口腔颌面部裂隙（NSOC）相关。
我们对从一个为非综合征性口腔颌面部裂隙GWAS建立的国际联盟中选取的中国人群中的806例非综合征性唇裂伴或不伴腭裂（NSCL/P）病例-父母三联体和202例非综合征性腭裂（NSCP）病例-父母三联体进行了分析。通过DNA样本和问卷收集基因型数据和母亲的环境暴露情况。采用条件逻辑回归模型，使用R软件中的trio包探索基因-基因相互作用和基因-环境相互作用。使用Bonferroni校正将显著性水平阈值设定为3.47×10。
分别在NSCL/P三联体和NSCP三联体中，七个基因中的总共144个单核苷酸多态性（SNP）通过了质量控制过程。经Bonferroni校正后，共有六对SNP相互作用显示出具有统计学意义的SNP-SNP相互作用（<3.47×10），在NSCL/P三联体中为rs7618735（）和rs
10848543（）、rs631948（）和rs556874（）以及rs631948（）和rs472631（）；在NSCP三联体中分别为rs589149（）和rs476
5834（）、rs1402704（）和rs358792（）以及rs1402704（）和rs358793（）。此外，在NSCL/P三联体和NSCP三联体的基因-环境相互作用分析中均未发现显著结果。
尽管本研究未能检测到基于七个WNT信号通路基因的基因-环境相互作用与NSOC风险之间的显著关联，但WNT信号通路基因可能通过潜在的基因-基因相互作用影响NSOC的风险。
