Gene-gene interaction among cell adhesion genes and risk of nonsyndromic cleft lip with or without cleft palate in Chinese case-parent trios.
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ABSTRACT: BACKGROUND:Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with complex etiology. One strategy for studying the genetic risk factors of NSCL/P is to consider gene-gene interaction (G × G) among gene pathways having a role in craniofacial development. The present study aimed to investigate the G × G among cell adhesion gene pathway. METHODS:We carried out an interaction analysis of eight genes involved in cell adherens junctions among 806 NSCL/P Chinese case-parent trios originally recruited for a genome-wide association study (GWAS). Regression-based approach was used to test for two-way G × G interaction, while machine learning algorithm was run for exploring both two-way and multi-way interaction that may affect the risk of NSCL/P. RESULTS:A two-way ACTN1 × CTNNB1 interaction reached the adjusted significance level. The single nucleotide polymorphisms pair composed of rs17252114 (CTNNB1) and rs1274944 (ACTN1) yielded a p value of .0002, and this interaction was also supported by the logic regression algorithm. Higher order interactions involving ACTN1, CTNNB1, and CDH1 were picked out by logic regression, suggesting a potential role in NSCL/P risk. CONCLUSION:This study suggests for the first time evidence of both two-way and multi-way G × G interactions among cell adhesion genes contributing to the NSCL/P risk.
SUBMITTER: Liu D
PROVIDER: S-EPMC6785639 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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