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      <jats:p>\n                    Nonsyndromic cleft lip with or without cleft palate (NSCL\/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene\u2010by\u2010sex (G\u2009\u00d7\u2009S) interactions in a worldwide sample of 2,142 NSCL\/P cases and 1,700 controls recruited from 13 countries. First, we performed genome\u2010wide joint tests of the genetic (G) and G\u2009\u00d7\u2009S effects genome\u2010wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20091.00\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ) by examining the G\u2009\u00d7\u2009S effects from the same model. Out of the 133 loci with suggestive results (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20091.00\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ) for the joint test, we observed one genome\u2010wide significant G\u2009\u00d7\u2009S effect in the 10q21 locus (rs72804706;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20096.69\u2009\u00d7\u200910\n                    <jats:sup>\u22129<\/jats:sup>\n                    ; OR\u2009=\u20092.62 CI [1.89, 3.62]) and 16 suggestive G\u2009\u00d7\u2009S effects. At the intergenic 10q21 locus, the risk of NSCL\/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL\/P risk differs for males and females may further our understanding of the genetic architecture of NSCL\/P and the sex differences underlying clefts and other birth defects.\n                  <\/jats:p>","DOI":"10.1002\/gepi.22158","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T02:03:07Z","timestamp":1536717787000},"page":"664-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Genome\u2010wide interaction studies identify sex\u2010specific risk alleles for nonsyndromic orofacial clefts"],"prefix":"10.1002","volume":"42","author":[{"given":"Jenna C.","family":"Carlson","sequence":"first","affiliation":[{"name":"Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Biostatistics Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole L.","family":"Nidey","sequence":"additional","affiliation":[{"name":"Department of Epidemiology College of Public Health, University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azeez","family":"Butali","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine Dows Institute for Dental Research, College of Dentistry, University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen J.","family":"Buxo","sequence":"additional","affiliation":[{"name":"Dental and Craniofacial Genomics Core School of Dental Medicine, University of Puerto Rico San Juan Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaare","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Institute of Public Health, University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic W.\u2010D.","family":"Deleyiannis","sequence":"additional","affiliation":[{"name":"Department of Surgery, Plastic and Reconstructive Surgery Division University of Colorado School of Medicine Denver Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline T.","family":"Hecht","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McGovern Medical School and School of Dentistry, UT Health at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Leigh","family":"Field","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina M.","family":"Moreno\u2010Uribe","sequence":"additional","affiliation":[{"name":"Department of Orthodontics College of Dentistry, University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieda M.","family":"Orioli","sequence":"additional","affiliation":[{"name":"ECLAMC (Latin American Collaborative Study of Congenital Malformations) at INAGEMP (National Institute of Population Medical Genetics)  Rio de Janeiro Brazil"},{"name":"Department of Genetics Institute of Biology, Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Poletta","sequence":"additional","affiliation":[{"name":"ECLAMC (Latin American Collaborative Study of Congenital Malformations) at INAGEMP (National Institute of Population Medical Genetics)  Rio de Janeiro Brazil"},{"name":"CEMIC\u2010CONICET: Center for Medical Education and Clinical Research \"Norberto Quirno\" Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmencita","family":"Padilla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine, University of the Philippines Manila Philippines"},{"name":"The Philippine Genome Center, University of the Philippines System Manilla Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre R.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Oral Biology Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Oral Biology Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Wehby","sequence":"additional","affiliation":[{"name":"Department of Health Management and Policy College of Public Health, University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Feingold","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Biostatistics Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Carver College of Medicine, University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Marazita","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Oral Biology Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-1712","authenticated-orcid":false,"given":"Elizabeth J.","family":"Leslie","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine, Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20595"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001435"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_2_6_1_7_1","first-page":"1","article-title":"Sexual differences in closure of the human palatal shelves","volume":"6","author":"Burdi A. 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