Open AccessGene–gene interaction among cell adhesion genes and risk of nonsyndromic cleft lip with or without cleft palate in Chinese case‐parent trios
Author(s) -
Liu Dongjing,
Wang Mengying,
Yuan Yuan,
Schwender Holger,
Wang Hong,
Wang Ping,
Zhou Zhibo,
Li Jing,
Wu Tao,
Zhu Hongping,
Beaty Terri H.
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.872
Subject(s) - craniofacial , gene , genetics , genome wide association study , adherens junction , single nucleotide polymorphism , bioinformatics , biology , medicine , cell , cadherin , genotype
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.