{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T22:54:05Z","timestamp":1767480845276,"version":"3.37.3"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T00:00:00Z","timestamp":1524528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["R01\u2010DE\u2010014581","81102178","81573225"],"award-info":[{"award-number":["R01\u2010DE\u2010014581","81102178","81573225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7172115"],"award-info":[{"award-number":["7172115"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Little consistent evidence is available for the association between the risk of non\u2010syndromic cleft lip with or without cleft palate (<jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/P) and any of the individual genes in the folate\/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/P considering gene\u2013gene (G\u00d7G) interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and methods<\/jats:title><jats:p>We selected markers in 18 genes from the pathway and applied Cordell's method to test for G\u00d7G interaction using 1,908 <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/P case\u2013parent trios ascertained in an international consortium where a genomewide association study (<jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content>) of oral clefts was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found intriguing signals among Asian and European ancestry groups for G\u00d7G interaction between markers in betaine\u2010homocysteine methyltransferase gene (<jats:italic><jats:styled-content style=\"fixed-case\">BHMT<\/jats:styled-content><\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">BHMT<\/jats:styled-content>2<\/jats:italic>) and dimethylglycine dehydrogenase gene (<jats:italic><jats:styled-content style=\"fixed-case\">DMGDH<\/jats:styled-content>)<\/jats:italic> attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (<jats:italic><jats:styled-content style=\"fixed-case\">BHMT<\/jats:styled-content><\/jats:italic>) and rs10514154 (<jats:italic><jats:styled-content style=\"fixed-case\">DMGDH<\/jats:styled-content><\/jats:italic>,<jats:italic> p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>1.45\u00a0\u00d7\u00a010<jats:sup>\u221212<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study illustrated the importance of taking into account potential G\u00d7G interaction for genetic association analysis in <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/P, and this study suggested both <jats:italic><jats:styled-content style=\"fixed-case\">BHMT<\/jats:styled-content><\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">BHMT<\/jats:styled-content>2<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">DMGDH<\/jats:styled-content><\/jats:italic> should be considered as candidate genes for <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/P in future studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12831","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T15:25:48Z","timestamp":1516634748000},"page":"820-828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Evidence of interaction between genes in the folate\/homocysteine metabolic pathway in controlling risk of non\u2010syndromic oral cleft"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0069-5458","authenticated-orcid":false,"given":"P","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health Peking University Beijing China"},{"name":"Department of Statistics and Information Beijing Center for Disease Prevention and Control &amp; Beijing Research Center for Preventive Medicine Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Wu","sequence":"additional","affiliation":[{"name":"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":"H","family":"Schwender","sequence":"additional","affiliation":[{"name":"Mathematical Institute Heinrich Heine University Duesseldorf Duesseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Disease West China School of Stomatology Sichuan University Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZQ","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DJ","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MY","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Li","sequence":"additional","affiliation":[{"name":"Pediatric Dentistry Peking University School of Stomatology Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZB","family":"Zhou","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Peking University School of Stomatology Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HP","family":"Zhu","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Peking University School of Stomatology Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"TH","family":"Beaty","sequence":"additional","affiliation":[{"name":"School of Public Health Johns Hopkins University Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20315"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20595"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31579"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20737"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.20.2463"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2579"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.10307"},{"issue":"2","key":"e_1_2_7_12_1","first-page":"e219","article-title":"New insights from GWAS for the cleft palate among han Chinese population","volume":"22","author":"Duan S. 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