{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:19:24Z","timestamp":1777522764842,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The Cleft Palate Craniofacial Journal"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nonsyndromic cleft lip with or without cleft palate (nsCL\u00b1P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated gene-environment and gene-gene joint effects in a large multicenter study of case-parent triads.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The nsCL\u00b1P or nsCP triads were recruited in 11 European countries between 2001 and 2005. We collected DNA samples from infants and from their mothers and fathers, and mothers completed a questionnaire on exposures, including smoking and folic acid supplement use during pregnancy. We used log-linear regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between nsCL\u00b1P or nsCP and variants in MTHFR, MTHFD1, TGFA, SATB2, and MSX1, stratifying by environmental or genetic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We obtained genotype and exposure data for 728 nsCL\u00b1P triads and 292 nsCP triads. In male infants, there was no association between the mother's homozygous MSX1 p(CA)\n                      <jats:sup>\u2217<\/jats:sup>\n                      4\/\n                      <jats:sup>\u2217<\/jats:sup>\n                      4 genotype and nsCL\u00b1P (RR, 0.98; 95% CI, 0.63\u20131.54), but this maternal genotype resulted in a doubling of risk for female infants (RR, 2.21; 95% CI, 1.13\u20134.34). There was evidence suggestive of gene-gene joint-effects between MTHFR-TGFA for nsCP but not for nsCL\u00b1P.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although we chose the genes and their variants and putative joint effects based on associations previously reported in the literature, we replicated few associations. These results do not provide evidence supporting associations between these genes and oral clefts in European populations, although gene-environment and gene-gene interactions could play a role in oral cleft etiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1597\/16-037","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T11:03:59Z","timestamp":1482231839000},"page":"623-630","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic Interactions in Nonsyndromic Orofacial Clefts in Europe\u2014EUROCRAN Study"],"prefix":"10.1177","volume":"54","author":[{"given":"Peter A.","family":"Mossey","sequence":"first","affiliation":[{"name":"Craniofacial Development at the World Health Organization\u2013collaborating Centre for Oral and Craniofacial Research, Dental Hospital and School, University of Dundee, Dundee, Scotland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Little","sequence":"additional","affiliation":[{"name":"School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regine","family":"Steegers-Theunissen","sequence":"additional","affiliation":[{"name":"Periconception Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Molloy","sequence":"additional","affiliation":[{"name":"Trinity Biomedical Sciences Institute, Dublin, Ireland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical Genetics, Department of Obstetrics & Gynecology, University Medical Center Ljubljana, Ljubljana, Slovenia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Orthodontics and Dentofacial Development, Manchester University Dental Hospital, Manchester, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice","family":"Johnson","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Cincinnati, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"FitzPatrick","sequence":"additional","affiliation":[{"name":"University of Edinburgh Western General Hospital, Edinburgh, Scotland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Franceschelli","sequence":"additional","affiliation":[{"name":"University of Ferrara, Ferrara, Italy, and is seconded to the University of Dundee, Dundee, Scotland, through the EUROCleftNet Exchange Visit Grant."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Rubini","sequence":"additional","affiliation":[{"name":"University of Ferrara, Ferrara, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"bibr1-16-037","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2013.04.022"},{"key":"bibr2-16-037","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"bibr3-16-037","first-page":"469","volume":"35","author":"Beaty T.H.","year":"2011","journal-title":"Genet 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