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 As a Clefting Susceptibility Gene

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2019 Dec 11

PMID 31817908

Citations 19

Authors

Iris Alm van Rooij

Kerstin U Ludwig

Julia Welzenbach

Nina Ishorst

Michelle Thonissen

Tessel E Galesloot

Edwin Ongkosuwito

Stefaan J Berge

Khalid Aldhorae

Augusto Rojas-Martinez

Lambertus Alm Kiemeney

Joris Robert Vermeesch

Han Brunner

Nel Roeleveld

Koen Devriendt

Titiaan Dormaar

Greet Hens

Michael Knapp

Carine Carels

Elisabeth Mangold

Affiliations

Soon will be listed here.

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 (-value of the lead SNV: 4.17 × 10). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized 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 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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