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Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants

Dupuytren disease (DD), a fibroproliferative disorder of the palmar fascia that causes flexion contractures in the fingers, is prevalent in people of North-Western European descent and less so in other ethnicities. DD is a complex disorder, influenced by genetic risk variants. We aimed to study if t...

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Autores principales: Riesmeijer, Sophie A., Werker, Paul M. N., Nolte, Ilja M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871523/
https://www.ncbi.nlm.nih.gov/pubmed/31363186
http://dx.doi.org/10.1038/s41431-019-0483-5
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author Riesmeijer, Sophie A.
Werker, Paul M. N.
Nolte, Ilja M.
author_facet Riesmeijer, Sophie A.
Werker, Paul M. N.
Nolte, Ilja M.
author_sort Riesmeijer, Sophie A.
collection PubMed
description Dupuytren disease (DD), a fibroproliferative disorder of the palmar fascia that causes flexion contractures in the fingers, is prevalent in people of North-Western European descent and less so in other ethnicities. DD is a complex disorder, influenced by genetic risk variants. We aimed to study if the marked differences in prevalences in DD between ethnic (sub)groups could be explained by differences in allele frequencies of the 26 known genetic risk variants of DD. Therefore, genetic risk scores (GRS) composed of the 26 DD risk variants were calculated for the 26 populations from the 1000 Genomes database and correlated to observed DD prevalences from literature. For comparison, GRSs were generated for 10,000 sets of 26 random SNPs and also correlated to the observed DD prevalences to determine the significance of the observed correlation. To determine whether differences in allele frequencies between ethnicities were caused by natural selection, fixation indices (Fst) were calculated from the 26 SNPs and from the sets of 26 random SNPs for comparison. Observed prevalences could be determined from literature for 10 populations. Their correlation with the GRS composed of DD SNPs proved to be 0.60 (p = 0.0003). The Fsts between British and other populations were low for European, ad mixed American, and South-Asian populations, and moderate for East-Asians. African populations were significantly different from expected values determined from the random sets. In conclusion, the 26 known genetic risk variants associated with DD explain for a substantial part (R(2) = 0.36) the differing DD prevalences observed between ethnicities.
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spelling pubmed-68715232019-11-25 Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants Riesmeijer, Sophie A. Werker, Paul M. N. Nolte, Ilja M. Eur J Hum Genet Article Dupuytren disease (DD), a fibroproliferative disorder of the palmar fascia that causes flexion contractures in the fingers, is prevalent in people of North-Western European descent and less so in other ethnicities. DD is a complex disorder, influenced by genetic risk variants. We aimed to study if the marked differences in prevalences in DD between ethnic (sub)groups could be explained by differences in allele frequencies of the 26 known genetic risk variants of DD. Therefore, genetic risk scores (GRS) composed of the 26 DD risk variants were calculated for the 26 populations from the 1000 Genomes database and correlated to observed DD prevalences from literature. For comparison, GRSs were generated for 10,000 sets of 26 random SNPs and also correlated to the observed DD prevalences to determine the significance of the observed correlation. To determine whether differences in allele frequencies between ethnicities were caused by natural selection, fixation indices (Fst) were calculated from the 26 SNPs and from the sets of 26 random SNPs for comparison. Observed prevalences could be determined from literature for 10 populations. Their correlation with the GRS composed of DD SNPs proved to be 0.60 (p = 0.0003). The Fsts between British and other populations were low for European, ad mixed American, and South-Asian populations, and moderate for East-Asians. African populations were significantly different from expected values determined from the random sets. In conclusion, the 26 known genetic risk variants associated with DD explain for a substantial part (R(2) = 0.36) the differing DD prevalences observed between ethnicities. Springer International Publishing 2019-07-30 2019-12 /pmc/articles/PMC6871523/ /pubmed/31363186 http://dx.doi.org/10.1038/s41431-019-0483-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Riesmeijer, Sophie A.
Werker, Paul M. N.
Nolte, Ilja M.
Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title_full Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title_fullStr Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title_full_unstemmed Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title_short Ethnic differences in prevalence of Dupuytren disease can partly be explained by known genetic risk variants
title_sort ethnic differences in prevalence of dupuytren disease can partly be explained by known genetic risk variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871523/
https://www.ncbi.nlm.nih.gov/pubmed/31363186
http://dx.doi.org/10.1038/s41431-019-0483-5
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