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One strategy for studying the genetic risk factors of NSCL\/P is to consider gene\u2013gene interaction (G\u00a0\u00d7\u00a0G) among gene pathways having a role in craniofacial development. The present study aimed to investigate the G\u00a0\u00d7\u00a0G among cell adhesion gene pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We carried out an interaction analysis of eight genes involved in cell adherens junctions among 806 NSCL\/P Chinese case\u2010parent trios originally recruited for a genome\u2010wide association study (GWAS). Regression\u2010based approach was used to test for two\u2010way G\u00a0\u00d7\u00a0G interaction, while machine learning algorithm was run for exploring both two\u2010way and multi\u2010way interaction that may affect the risk of NSCL\/P.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two\u2010way <jats:italic>ACTN1<\/jats:italic>\u00a0\u00d7\u00a0<jats:italic>CTNNB1<\/jats:italic> interaction reached the adjusted significance level. The single nucleotide polymorphisms pair composed of rs17252114 (<jats:italic>CTNNB1<\/jats:italic>) and rs1274944 (<jats:italic>ACTN1<\/jats:italic>) yielded a <jats:italic>p<\/jats:italic> value of .0002, and this interaction was also supported by the logic regression algorithm. Higher order interactions involving <jats:italic>ACTN1<\/jats:italic>, <jats:italic>CTNNB1<\/jats:italic>, and <jats:italic>CDH1<\/jats:italic> were picked out by logic regression, suggesting a potential role in NSCL\/P risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study suggests for the first time evidence of both two\u2010way and multi\u2010way G\u00a0\u00d7\u00a0G interactions among cell adhesion genes contributing to the NSCL\/P risk.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.872","type":"journal-article","created":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T13:05:08Z","timestamp":1565960708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gene\u2013gene interaction among cell adhesion genes and risk of nonsyndromic cleft lip with or without cleft palate in Chinese case\u2010parent trios"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-7789","authenticated-orcid":false,"given":"Dongjing","family":"Liu","sequence":"first","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Schwender","sequence":"additional","affiliation":[{"name":"Mathematical Institute Heinrich Heine University Duesseldorf Duesseldorf 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