PUBLICATION
Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene
- Authors
- van Rooij, I.A., Ludwig, K.U., Welzenbach, J., Ishorst, N., Thonissen, M., Galesloot, T.E., Ongkosuwito, E., Bergé, S.J., Aldhorae, K., Rojas-Martinez, A., Kiemeney, L.A., Vermeesch, J.R., Brunner, H., Roeleveld, N., Devriendt, K., Dormaar, T., Hens, G., Knapp, M., Carels, C., Mangold, E.
- ID
- ZDB-PUB-191212-21
- Date
- 2019
- Source
- Genes 10(12): (Journal)
- Registered Authors
- Ishorst, Nina
- Keywords
- cleft lip with or without cleft palate, congenital malformation, genome-wide association study, orofacial cleft
- MeSH Terms
-
- Adaptor Proteins, Vesicular Transport/genetics*
- Animals
- Belgium
- Chromosomes, Human, Pair 10/genetics
- Chromosomes, Human, Pair 16/genetics*
- Cleft Lip/genetics*
- Cleft Palate/genetics*
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mice
- Mice, Knockout
- Netherlands
- Risk Factors
- Zebrafish
- PubMed
- 31817908 Full text @ Genes (Basel)
Citation
van Rooij, I.A., Ludwig, K.U., Welzenbach, J., Ishorst, N., Thonissen, M., Galesloot, T.E., Ongkosuwito, E., Bergé, S.J., Aldhorae, K., Rojas-Martinez, A., Kiemeney, L.A., Vermeesch, J.R., Brunner, H., Roeleveld, N., Devriendt, K., Dormaar, T., Hens, G., Knapp, M., Carels, C., Mangold, E. (2019) Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene. Genes. 10(12):.
Abstract
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 × 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping