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This study investigates distinct facial morphology among unaffected relatives and examines whether candidate genes previously associated with overt <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> and left\u2013right body patterning are correlated with such facial morphology. Cases were unaffected relatives of individuals with <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a0188) and controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a0194) were individuals without family history of <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>. Cases and controls were genotyped for 20 <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s across 13 candidate genes for <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> (<jats:italic>PAX7, ABCA4\u2010ARHGAP29, IRF6, MSX1, PITX2,<\/jats:italic> 8q24<jats:italic>, FOXE1, TGFB3<\/jats:italic> and <jats:italic>MAFB<\/jats:italic>) and left\u2013right body patterning (<jats:italic>LEFTY1, LEFTY2, ISL1 and SNAI1<\/jats:italic>). Facial shape and asymmetry phenotypes were obtained via principal component analyses and Procrustes analysis of variance from 32 coordinate landmarks, digitized on 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> facial images. Case\u2013control comparisons of phenotypes obtained were performed via multivariate regression adjusting for age and gender. Phenotypes that differed significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) between cases and controls were regressed on the <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s one at a time. Cases had significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) more profile concavity with upper face retrusion, upturned noses with obtuse nasolabial angles, more protrusive chins, increased lower facial heights, thinner and more retrusive lips and more protrusive foreheads. Furthermore, cases showed significantly more directional asymmetry compared to controls. Several of these phenotypes were significantly associated with genetic variants (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Facial height and width were associated with <jats:italic>SNAI1<\/jats:italic>. Midface antero\u2010posterior (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>) projection was associated with <jats:italic>LEFTY1<\/jats:italic>. The <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> position of the chin was related to <jats:italic>SNAI1, IRF6<\/jats:italic>,<jats:italic> MSX1 and MAFB<\/jats:italic>. The <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> position of the forehead and the width of the mouth were associated with <jats:italic>ABCA4\u2013ARHGAP29<\/jats:italic> and <jats:italic>MAFB<\/jats:italic>. Lastly, facial asymmetry was related to <jats:italic>LEFTY1, LEFTY2 and SNAI1<\/jats:italic>. This study demonstrates that, genes underlying lip and palate formation and left\u2013right patterning also contribute to facial features characteristic of the <jats:styled-content style=\"fixed-case\">NSCL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> spectrum.<\/jats:p>","DOI":"10.1111\/joa.12182","type":"journal-article","created":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T02:41:26Z","timestamp":1397702486000},"page":"688-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Exploratory genotype\u2013phenotype correlations of facial form and asymmetry in unaffected relatives of children with non\u2010syndromic cleft lip and\/or palate"],"prefix":"10.1111","volume":"224","author":[{"given":"Steven F.","family":"Miller","sequence":"first","affiliation":[{"name":"Dows Institute for Dental Research College of Dentistry University of Iowa Iowa City IA 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