Author(s):
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Rooij, I.A.L.M. van
; Ludwig, K.U.; Welzenbach, J.; Ishorst, N.; Thonissen, M.;
Galesloot, T.E.
;
Ongkosuwito, E.M.
;
Berge, S.J.
; Aldhorae, K.; Rojas-Martinez, A.;
Kiemeney, L.A.
; Vermeesch, J.R.;
Brunner, H.G.
;
Roeleveld, N.
; Devriendt, K.; Dormaar, T.; Hens, G.; Knapp, M.;
Carels, C.E.
; Mangold, E.
|
Subject:
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Radboudumc 10: Reconstructive and regenerative medicine RIHS: Radboud Institute for Health Sciences Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience Tijdelijke code tbv inlezen publicaties Radboudumc - Alleen voor gebruik door Radboudumc |
Organization:
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Health Evidence Dentistry Oral and Maxillofacial Surgery Urology Human Genetics Molecular Developmental Biology |
Abstract:
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Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 x 10(-7)). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.
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