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Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals

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 co...

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Autores principales: Ågren, Richard, Patil, Snehal, Zhou, Xiang, Sahlholm, Kristoffer, Pääbo, Svante, Zeberg, Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266526/
https://www.ncbi.nlm.nih.gov/pubmed/37315093
http://dx.doi.org/10.1093/molbev/msad130
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author Ågren, Richard
Patil, Snehal
Zhou, Xiang
Sahlholm, Kristoffer
Pääbo, Svante
Zeberg, Hugo
author_facet Ågren, Richard
Patil, Snehal
Zhou, Xiang
Sahlholm, Kristoffer
Pääbo, Svante
Zeberg, Hugo
author_sort Ågren, Richard
collection PubMed
description 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.
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spelling pubmed-102665262023-06-15 Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals Ågren, Richard Patil, Snehal Zhou, Xiang Sahlholm, Kristoffer Pääbo, Svante Zeberg, Hugo Mol Biol Evol Discoveries 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. Oxford University Press 2023-06-14 /pmc/articles/PMC10266526/ /pubmed/37315093 http://dx.doi.org/10.1093/molbev/msad130 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Discoveries
Ågren, Richard
Patil, Snehal
Zhou, Xiang
Sahlholm, Kristoffer
Pääbo, Svante
Zeberg, Hugo
Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title_full Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title_fullStr Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title_full_unstemmed Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title_short Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
title_sort major genetic risk factors for dupuytren's disease are inherited from neandertals
topic Discoveries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266526/
https://www.ncbi.nlm.nih.gov/pubmed/37315093
http://dx.doi.org/10.1093/molbev/msad130
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