Universität zu Köln

Ishorst, Nina, Francheschelli, Paola, Boehmer, Anne C., Khan, Mohammad Faisal J., Heilmann-Heimbach, Stefanie ORCID: 0000-0003-1057-465X, Fricker, Nadine, Little, Julian ORCID: 0000-0001-5026-5531, Steegers-Theunissen, Regine P. M., Peterlin, Borut, Nowak, Stefanie, Martini, Markus, Kruse, Teresa, Dunsche, Anton, Kreusch, Thomas, Goelz, Lina, Aldhorae, Khalid ORCID: 0000-0002-5920-8004, Halboub, Esam ORCID: 0000-0002-1894-470X, Reutter, Heiko, Mossey, Peter, Noethen, Markus M., Rubini, Michele ORCID: 0000-0003-1448-9516, Ludwig, Kerstin U., Knapp, Michael and Mangold, Elisabeth (2018). Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample. Birth Defects Res., 110 (10). S. 871 - 883. HOBOKEN: WILEY. ISSN 2472-1727

Full text not available from this repository.

Abstract

BackgroundNonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. MethodsWe genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family-based sample of European ancestry (n=212); and (ii) two case/control samples of Central European (n=94/339) and Arabian ancestry (n=38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta-analyses were performed. ResultsAfter association analysis and meta-analyses, none of the 33 SNPs showed genome-wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p-value in a European and an overall meta-analysis including imputed GWAS data, respectively (rs395572: P-MetaEU=3.16 x 10(-4); rs6809420: P-MetaAll=2.80 x 10(-4)). ConclusionOur findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome-wide significant loci. Whole-exome/genome sequencing studies of nsCPO are now warranted.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ishorst, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Francheschelli, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehmer, Anne C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Khan, Mohammad Faisal J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann-Heimbach, Stefanie UNSPECIFIED orcid.org/0000-0003-1057-465X UNSPECIFIED Fricker, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Little, Julian UNSPECIFIED orcid.org/0000-0001-5026-5531 UNSPECIFIED Steegers-Theunissen, Regine P. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peterlin, Borut UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowak, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Martini, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kruse, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Dunsche, Anton UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreusch, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Goelz, Lina UNSPECIFIED UNSPECIFIED UNSPECIFIED Aldhorae, Khalid UNSPECIFIED orcid.org/0000-0002-5920-8004 UNSPECIFIED Halboub, Esam UNSPECIFIED orcid.org/0000-0002-1894-470X UNSPECIFIED Reutter, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Mossey, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Noethen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubini, Michele UNSPECIFIED orcid.org/0000-0003-1448-9516 UNSPECIFIED Ludwig, Kerstin U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knapp, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Mangold, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-185034
DOI:	10.1002/bdr2.1213
Journal or Publication Title:	Birth Defects Res.
Volume:	110
Number:	10
Page Range:	S. 871 - 883
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2472-1727
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; OROFACIAL CLEFTS; SUSCEPTIBILITY LOCUS; BINDING-SITE; RISK LOCI; LIP; IDENTIFY; FOXE1; METAANALYSES; EFFICIENT Multiple languages Developmental Biology; Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18503