A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease

Sophie A. Riesmeijer (), Zoha Kamali, Michael Ng, Dmitriy Drichel, Bram Piersma, Kerstin Becker, Thomas B. Layton, Jagdeep Nanchahal, Michael Nothnagel, Ahmad Vaez, Hans Christian Hennies, Paul M. N. Werker, Dominic Furniss and Ilja M. Nolte
Additional contact information
Sophie A. Riesmeijer: University of Groningen, University Medical Center Groningen, Department of Plastic Surgery
Zoha Kamali: University of Groningen, University Medical Center Groningen, Department of Epidemiology
Michael Ng: University of Oxford
Dmitriy Drichel: University of Cologne
Bram Piersma: University of Groningen
Kerstin Becker: University of Cologne
Thomas B. Layton: University of Oxford
Jagdeep Nanchahal: University of Oxford
Michael Nothnagel: University of Cologne
Ahmad Vaez: University of Groningen, University Medical Center Groningen, Department of Epidemiology
Hans Christian Hennies: Faculty of Medicine and the Cologne University Hospital
Paul M. N. Werker: University of Groningen, University Medical Center Groningen, Department of Plastic Surgery
Dominic Furniss: University of Oxford
Ilja M. Nolte: University of Groningen, University Medical Center Groningen, Department of Epidemiology

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Dupuytren’s disease (DD) is a highly heritable fibrotic disorder of the hand with incompletely understood etiology. A number of genetic loci, including Wnt signaling members, have been previously identified. Our overall aim was to identify novel genetic loci, to prioritize genes within the loci for functional studies, and to assess genetic correlation with associated disorders. We performed a meta-analysis of six DD genome-wide association studies from three European countries and extensive bioinformatic follow-up analyses. Leveraging 11,320 cases and 47,023 controls, we identified 85 genome-wide significant single nucleotide polymorphisms in 56 loci, of which 11 were novel, explaining 13.3–38.1% of disease variance. Gene prioritization implicated the Hedgehog and Notch signaling pathways. We also identified a significant genetic correlation with frozen shoulder. The pathways identified highlight the potential for new therapeutic targets and provide a basis for additional mechanistic studies for a common disorder that can severely impact hand function.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44451-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44451-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44451-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().