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, Ilja M Nolte

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
32 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummer199
Aantal pagina's11
TijdschriftNature Communications
Volume15
DOI's
StatusPublished - 3-jan.-2024

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