{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:42:01Z","timestamp":1777909321240,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T00:00:00Z","timestamp":1449619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["grant FOR 423 and individual grants MA 2546\/3-1, KR 1912\/7-1, NO 246\/6-1, and WI 1555\/5-1"],"award-info":[{"award-number":["grant FOR 423 and individual grants MA 2546\/3-1, KR 1912\/7-1, NO 246\/6-1, and WI 1555\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"BONFOR-program of the Medical Faculty of the University of Bonn","award":["O-149.0097"],"award-info":[{"award-number":["O-149.0097"]}]},{"name":"Interethnos-Interplast Association, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Nonsyndromic cleft lip with or without cleft palate (nsCL\/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL\/P loci using an independent sample of the Italian population.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>At least one single\u2010nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (<jats:italic>P<\/jats:italic><jats:sub>TDT<\/jats:sub>\u2009=\u20096.81 \u00d7 10<jats:sup>\u22126<\/jats:sup>; homozygous relative risk\u2009=\u20093.60 [95% confidence interval, 2.12\u20136.13]), and the rs17241253 (<jats:italic>P<\/jats:italic><jats:sub>TDT<\/jats:sub>\u2009=\u20091.03 \u00d7 10<jats:sup>\u22125<\/jats:sup>; homozygous relative risk\u2009=\u20093.75 [95% confidence interval, 2.10\u20136.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant<jats:italic>p<\/jats:italic>\u2010values. Two SNPs at 1p36 achieved<jats:italic>p<\/jats:italic>\u2010values of\u2009&lt;\u20090.1. The present data suggest that 6 of the 15 analyzed nsCL\/P risk loci contribute significantly to nsCL\/P risk in the Italian population. These include the 1p22 locus, which previous research has implicated predominantly in Asian populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Different loci, including 8q24 and 1p22 have been found associated with nsCL\/P in multiple populations. Further efforts are needed to identify causative variants and transfer knowledge to clinical application, such as personal genetic risk assessment. Birth Defects Research (Part A) 106:81\u201387, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23454","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T01:06:17Z","timestamp":1449795977000},"page":"81-87","source":"Crossref","is-referenced-by-count":7,"title":["Replication analysis of 15 susceptibility loci for nonsyndromic cleft lip with or without cleft palate in an italian population"],"prefix":"10.1002","volume":"106","author":[{"given":"Francesca","family":"Cura","sequence":"first","affiliation":[{"name":"Department of Experimental Diagnostic and Specialty Medicine, University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne C.","family":"B\u00f6hmer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Klamt","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Sch\u00fcnke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Scapoli","sequence":"additional","affiliation":[{"name":"Department of Experimental Diagnostic and Specialty Medicine, University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Diagnostic and Specialty Medicine, University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Carinci","sequence":"additional","affiliation":[{"name":"Department of Morphology Surgery and Experimental Medicine, University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M.","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Knapp","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin U.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Mangold","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23221"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/424390"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1002\/ajmg.a.36141","article-title":"Analysis of susceptibility loci for nonsyndromic orofacial clefting in a European trio sample","volume":"161","author":"B\u00f6hmer AC","year":"2013","journal-title":"Am J Med Genet A"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23011"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.06.020"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02284-3"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23394"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23076"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.01.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23286"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514523987"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2360"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.506"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000224636"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/422475"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp444"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20687"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.242"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20689"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/427344"},{"key":"e_1_2_6_28_1","first-page":"1114","article-title":"Genotype relative risks: methods for design and analysis of candidate\u2010gene association studies","volume":"53","author":"Schaid DJ","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2971"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.11.004"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33940"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032909"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.23454","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T23:46:15Z","timestamp":1718235975000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,9]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1002\/bdra.23454"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23454","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,9]]}}}