A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic va...

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Autores principales:	Harry D Green, Alistair Jones, Jonathan P Evans, Andrew R Wood, Robin N Beaumont, Jessica Tyrrell, Timothy M Frayling, Christopher Smith, Michael N Weedon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/723863099c1743b796989aeca53ce1fa
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spelling	oai:doaj.org-article:723863099c1743b796989aeca53ce1fa2021-12-02T20:02:42ZA genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.1553-73901553-740410.1371/journal.pgen.1009577https://doaj.org/article/723863099c1743b796989aeca53ce1fa2021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009577https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.Harry D GreenAlistair JonesJonathan P EvansAndrew R WoodRobin N BeaumontJessica TyrrellTimothy M FraylingChristopher SmithMichael N WeedonPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 6, p e1009577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Harry D Green Alistair Jones Jonathan P Evans Andrew R Wood Robin N Beaumont Jessica Tyrrell Timothy M Frayling Christopher Smith Michael N Weedon A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
description	Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.
format	article
author	Harry D Green Alistair Jones Jonathan P Evans Andrew R Wood Robin N Beaumont Jessica Tyrrell Timothy M Frayling Christopher Smith Michael N Weedon
author_facet	Harry D Green Alistair Jones Jonathan P Evans Andrew R Wood Robin N Beaumont Jessica Tyrrell Timothy M Frayling Christopher Smith Michael N Weedon
author_sort	Harry D Green
title	A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
title_short	A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
title_full	A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
title_fullStr	A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
title_full_unstemmed	A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
title_sort	genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/723863099c1743b796989aeca53ce1fa
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A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.

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