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Major genetic risk factors for Dupuytren's disease are inherited from neandertals
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Biostatistics, University of Michigan, MI, Ann Arbor, United States.
Department of Biostatistics, University of Michigan, MI, Ann Arbor, United States.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0001-6536-1972
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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-211149DOI: 10.1093/molbev/msad130ISI: 001007768300001PubMedID: 37315093Scopus ID: 2-s2.0-85162012355OAI: oai:DiVA.org:umu-211149DiVA, id: diva2:1780849
Funder
Swedish Research Council, 2021-03050The Swedish Brain Foundation, PS2022-0040Erik Philip-Sörensens stiftelseHedlund foundationAvailable from: 2023-07-06 Created: 2023-07-06 Last updated: 2025-02-10Bibliographically approved

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Sahlholm, Kristoffer

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Department of Integrative Medical Biology (IMB)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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