Major genetic risk factors for Dupuytren's disease are inherited from neandertals Show others and affiliations
2023 (English) In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 40, no 6, article id msad130Article in journal (Refereed) Published
Abstract [en]
Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10-132 and P = 9.2 × 10-69 , respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.
Place, publisher, year, edition, pages Oxford University Press, 2023. Vol. 40, no 6, article id msad130
Keywords [en]
Dupuytren's disease, EPDR1, genome-wide association studies, Neandertals, risk variant, splicing quantitative trait loci
National Category
Medical Genetics and Genomics
Identifiers URN: urn:nbn:se:umu:diva-211149 DOI: 10.1093/molbev/msad130 ISI: 001007768300001 PubMedID: 37315093 Scopus ID: 2-s2.0-85162012355 OAI: oai:DiVA.org:umu-211149 DiVA, id: diva2:1780849
Funder Swedish Research Council, 2021-03050 The Swedish Brain Foundation, PS2022-0040 Erik Philip-Sörensens stiftelse Hedlund foundation 2023-07-062023-07-062025-02-10 Bibliographically approved