{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T22:54:20Z","timestamp":1740178460853,"version":"3.37.3"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T00:00:00Z","timestamp":1516147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["U01\u2010DE\u2010018993"],"award-info":[{"award-number":["U01\u2010DE\u2010018993"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81102178","81573225"],"award-info":[{"award-number":["81102178","81573225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Small ubiquitin\u2010like modification, also known as sumoylation, is a crucial post\u2010translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, <jats:italic>MSX1<\/jats:italic> and <jats:italic>TP63<\/jats:italic>, to have achieved genome\u2010wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene\u2013gene and gene\u2013environment interaction for <jats:italic>SUMO1<\/jats:italic>, <jats:italic>MSX1<\/jats:italic>, and <jats:italic>TP63<\/jats:italic> to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL\/P).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 130 single\u2010nucleotide polymorphisms (SNPs) in or near <jats:italic>SUMO1<\/jats:italic>, <jats:italic>MSX1<\/jats:italic>, and <jats:italic>TP63<\/jats:italic> was analyzed among 1,038 Asian NSCL\/P trios ascertained through an international consortium. Conditional logistic regression models were used to explore gene\u2013gene (G \u00d7 G) and gene\u2013environment (G \u00d7 E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G \u00d7 E analysis and permutation tests were used for G \u00d7 G analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While transmission disequilibrium tests and gene\u2013environment interaction analysis showed no significant results, we did find signals of gene\u2013gene interaction between SNPs near <jats:italic>MSX1<\/jats:italic> and <jats:italic>TP63<\/jats:italic>. Three pairwise interactions yielded significant <jats:italic>p<\/jats:italic> values in permutation tests (rs884690 and rs9290890 with <jats:italic>p<\/jats:italic>\u2009=\u20099.34 \u00d7 10<jats:sup>\u22125<\/jats:sup> and empirical <jats:italic>p<\/jats:italic>\u2009=\u20091.00 \u00d7 10<jats:sup>\u22124<\/jats:sup>, rs1022136 and rs4687098 with <jats:italic>p<\/jats:italic>\u2009=\u20092.41 \u00d7 10<jats:sup>\u22124<\/jats:sup> and empirical <jats:italic>p<\/jats:italic>\u2009=\u20092.95 \u00d7 10<jats:sup>\u22124<\/jats:sup>, rs6819546 and rs9681004 with <jats:italic>p<\/jats:italic>\u2009=\u20095.15 \u00d7 10<jats:sup>\u22124<\/jats:sup> and empirical <jats:italic>p<\/jats:italic>\u2009=\u20093.02 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Gene\u2013gene interaction between <jats:italic>MSX1<\/jats:italic> and <jats:italic>TP63<\/jats:italic> may influence the risk of NSCL\/P in Asian populations. Our study provided additional understanding of the genetic etiology of NSCL\/P and underlined the importance of considering gene\u2013gene interaction in the etiology of this common craniofacial malformation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1139","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T11:34:58Z","timestamp":1516188898000},"page":"317-324","source":"Crossref","is-referenced-by-count":6,"title":["Gene\u2013gene interaction between <i>MSX1<\/i> and <i>TP63<\/i> in Asian case\u2010parent trios with nonsyndromic cleft lip with or without cleft palate"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-7789","authenticated-orcid":false,"given":"Dongjing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Schwender","sequence":"additional","affiliation":[{"name":"Mathematical Institute, Heinrich Heine University Duesseldorf Duesseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-5355","authenticated-orcid":false,"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Statistics and Information Beijing Center for Disease Prevention and Control Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongping","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Stomatology Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibo","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Stomatology Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Stomatology Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking University Beijing China"},{"name":"Key Laboratory of Reproductive Health, Ministry of Health Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri H.","family":"Beaty","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health Johns Hopkins University Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290185"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128406"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-008-9136-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9503.1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20595"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.12.019"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng730"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81646-3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1597\/05-167"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.20.2463"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijporl.2010.10.005","article-title":"SUMO1 as a candidate gene for non\u2010syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients","volume":"75","author":"Assis N. 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