Universität zu Köln

Becker, Kerstin, Siegert, Sabine, Toliat, Mohammad Reza, Du, Juanjiangmeng, Casper, Ramona, Dolmans, Guido H., Werker, Paul M., Tinschert, Sigrid, Franke, Andre ORCID: 0000-0003-1530-5811, Gieger, Christian ORCID: 0000-0001-6986-9554, Strauch, Konstantin, Nothnagel, Michael ORCID: 0000-0001-8305-7114, Nuernberg, Peter and Hennies, Hans Christian (2016). Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren's Disease. PLoS One, 11 (7). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Dupuytren's disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren's disease, much of the inherited risk in Dupuytren's disease still needs to be discovered. The already identified loci jointly explain similar to 1% of the heritability in this disease. To further elucidate the genetic basis of Dupuytren's disease, we performed a genome-wide meta-analysis combining three genome-wide association study (GWAS) data sets, comprising 1,580 cases and 4,480 controls. We corroborated all nine previously identified loci, six of these with genome-wide significance (p-value < 5x10(-8)). In addition, we identified 14 new suggestive loci (p-value < 10(-5)). Intriguingly, several of these new loci contain genes associated with Wnt signalling and therefore represent excellent candidates for replication. Next, we compared whole-transcriptome data between patient- and control-derived tissue samples and found the Wnt/beta-catenin pathway to be the top deregulated pathway in patient samples. We then conducted network and pathway analyses in order to identify protein networks that are enriched for genes highlighted in the GWAS meta-analysis and expression data sets. We found further evidence that the Wnt signalling pathways in conjunction with other pathways may play a critical role in Dupuytren's disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Becker, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Siegert, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, Mohammad Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Du, Juanjiangmeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Casper, Ramona UNSPECIFIED UNSPECIFIED UNSPECIFIED Dolmans, Guido H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Werker, Paul M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tinschert, Sigrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Franke, Andre UNSPECIFIED orcid.org/0000-0003-1530-5811 UNSPECIFIED Gieger, Christian UNSPECIFIED orcid.org/0000-0001-6986-9554 UNSPECIFIED Strauch, Konstantin UNSPECIFIED UNSPECIFIED UNSPECIFIED Nothnagel, Michael UNSPECIFIED orcid.org/0000-0001-8305-7114 UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennies, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269489
DOI:	10.1371/journal.pone.0158101
Journal or Publication Title:	PLoS One
Volume:	11
Number:	7
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CONTRACTURE; HERITABILITY; INFORMATION; ALCOHOL; PATHWAY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26948