A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3

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dc.contributor.authorLeslie, E.J.
dc.contributor.authorLiu, H.
dc.contributor.authorCarlson, J.C.
dc.contributor.authorShaffer, J.R.
dc.contributor.authorFeingold, E.
dc.contributor.authorWehby, G.
dc.contributor.authorLaurie, C.A.
dc.contributor.authorJain, D.
dc.contributor.authorLaurie, C.C.
dc.contributor.authorDoheny, K.F.
dc.contributor.authorMcHenry, T.
dc.contributor.authorResick, J.
dc.contributor.authorSanchez, C.
dc.contributor.authorJacobs, J.
dc.contributor.authorEmanuele, B.
dc.contributor.authorVieira, A.R.
dc.contributor.authorNeiswanger, K.
dc.contributor.authorStandley, J.
dc.contributor.authorCzeizel, A.E.
dc.contributor.authorDeleyiannis, F.
dc.contributor.authorChristensen, K.
dc.contributor.authorMunger, R.G.
dc.contributor.authorLie, R.T.
dc.contributor.authorWilcox, A.
dc.contributor.authorRomitti, P.A.
dc.contributor.authorField, L.L.
dc.contributor.authorPadilla, C.D.
dc.contributor.authorCutiongco-de la Paz, E.M.
dc.contributor.authorLidral, A.C.
dc.contributor.authorValencia-Ramirez, L.C.
dc.contributor.authorLopez-Palacio, A.M.
dc.contributor.authorValencia, D.R.
dc.contributor.authorArcos-Burgos, M.
dc.contributor.authorCastilla, E.E.
dc.contributor.authorMereb, J.C.
dc.contributor.authorPoletta, F.A.
dc.contributor.authorOrioli, I.M.
dc.contributor.authorCarvalho, F.M.
dc.contributor.authorHecht, J.T.
dc.contributor.authorBlanton, S.H.
dc.contributor.authorBuxo, C.J.
dc.contributor.authorButali, A.
dc.contributor.authorAdeyemo, W.L.
dc.contributor.authorJames, O.
dc.contributor.authorBraimah, R.O.
dc.contributor.authorAregbesola, B.S.
dc.contributor.authorEshete, M.A.
dc.contributor.authorDeribew, M.
dc.contributor.authorKoruyucu, M.
dc.contributor.authorSeymen, F.
dc.contributor.authorMa, L.
dc.contributor.authorde Salamanca, J.E.
dc.contributor.authorWeinberg, S.M.
dc.contributor.authorMoreno, L.
dc.contributor.authorCornell, R.A.
dc.contributor.authorMurray, J.C.
dc.contributor.authorMarazita, M.L.
dc.date.accessioned2019-11-01T13:59:59Z
dc.date.available2019-11-01T13:59:59Z
dc.date.issued2016-04-01
dc.descriptionStaff publicationsen_US
dc.description.abstractCleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10(-9)) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.en_US
dc.identifier.citationA Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3. Leslie EJ, Liu H, Carlson JC, Shaffer JR, Feingold E, Wehby G, Laurie CA, Jain D, Laurie CC, Doheny KF, McHenry T, Resick J, Sanchez C, Jacobs J, Emanuele B, Vieira AR, Neiswanger K, Standley J, Czeizel AE, Deleyiannis F, Christensen K, Munger RG, Lie RT, Wilcox A, Romitti PA, Field LL, Padilla CD, Cutiongco-de la Paz EM, Lidral AC, Valencia-Ramirez LC, Lopez-Palacio AM, Valencia DR, Arcos-Burgos M, Castilla EE, Mereb JC, Poletta FA, Orioli IM, Carvalho FM, Hecht JT, Blanton SH, Buxó CJ, Butali A, Mossey PA, Adeyemo WL, James O, Braimah RO, Aregbesola BS, Eshete MA, Deribew M, Koruyucu M, Seymen F, Ma L, de Salamanca JE, Weinberg SM, Moreno L, Cornell RA, Murray JC, Marazita ML. Am J Hum Genet. 2016 Apr 7;98(4):744-54.en_US
dc.identifier.urihttps://ir.unilag.edu.ng/handle/123456789/6651
dc.language.isoenen_US
dc.publisherCellPressen_US
dc.subjectGWASen_US
dc.subjectGenome-wide Association Studyen_US
dc.subjectNon-syndromic cleft palateen_US
dc.subjectEtiologic Missense Varianten_US
dc.subjectGRHL3 geneen_US
dc.subjectResearch Subject Categories::ODONTOLOGYen_US
dc.titleA Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3en_US
dc.typeArticleen_US
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