{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:59:48Z","timestamp":1768802388147,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,15]]},"group-title":"Epidemiology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>Our understanding of the genetic causes of non-syndromic orofacial clefts (OFCs) is based largely upon genetic studies of common and rare nucleotide variants. Less is known about the role of copy number variations (CNVs) and the studies published to date have been limited to either small samples or targeted genomic regions. The objective of our study is to investigate the contribution of CNVs spread across the entire genome to OFC risk in a large multi-ancestry cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>We utilized PennCNV on microarray genotyping data to detect CNVs in 10,240 participants (2,484 with clefts, 7,756 unaffected). 70,695 quality-filtered autosomal CNVs (49,660 deletions, 21,035 duplications) were used to assign normal\/abnormal copy number statuses at 67,199 positions from the GRCh37 genome assembly. Genome-wide association was run between cleft status and copy number status.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>\n                    We observed a highly significant association between OFCs and deletions on chromosome 7p14.1 (p=1.32e-35) driven by Central and South American ancestry (p=1.04e-25) participants, with less significant contributions from European (p=3.37e-08) and Asian (p=0.01) ancestry participants. We also observed four other loci with\n                    <jats:italic>p<\/jats:italic>\n                    -values below 10e-04.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>The 7p14.1 association observed in our study is a replication of two prior studies in independent cohorts of European ancestry. However, this locus lies in a T-cell receptor region that is subject to somatic rearrangements that decrease in frequency with age and may affect genetic association results. Our data show age effects as well as differences between blood and saliva samples. Thus, our results can be interpreted either as supporting a previously established association with orofacial clefts, or as questioning those previous results in favor of a hypothesis about the behavior of somatic rearrangements in T-cell receptor regions.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.09.26343782","type":"posted-content","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:45:16Z","timestamp":1768524316000},"source":"Crossref","is-referenced-by-count":0,"title":["Is 7p14.1 an orofacial cleft risk locus? Genome-wide study of copy number variation in multiple populations provides both a replication of previous studies and an alternative explanation"],"prefix":"10.64898","author":[{"given":"Nandita","family":"Mukhopadhyay","sequence":"first","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor E.","family":"Feingold","sequence":"additional","affiliation":[{"name":"College of Science, Oregon State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harrison","family":"Brand","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Mass General Research Institute, Boston, MA 02114"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Surgery, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung Keun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edibe Nehir","family":"Kurtas","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Mass General Research Institute, Boston, MA 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Sanchis-Juan","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Mass General Research Institute, Boston, MA 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Moreno-Uribe","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, & The Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Wehby","sequence":"additional","affiliation":[{"name":"Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz Consuelo","family":"Valencia-Ramirez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Cl\u00ednica Noel; Calle 14 # 43B \u2013 146, Medell\u00edn, Antioquia, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia P.","family":"Restrepo Mu\u00f1eton","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Cl\u00ednica Noel; Calle 14 # 43B \u2013 146, Medell\u00edn, Antioquia, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmencita","family":"Padilla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila, the Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Deleyiannis","sequence":"additional","affiliation":[{"name":"UCHealth Medical Group, Colorado Springs, CO. 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