A molecular quantitative trait locus map for osteoarthritis

Abstract

Osteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools and modifying therapies, we need a better understanding of the molecular basis of the disease in relevant tissue and cell types. Here, we study primary cartilage and synovium from 115 patients with osteoarthritis to construct a deep molecular signature map of the disease. By integrating genetics with transcriptomics and proteomics, we discover molecular trait loci in each tissue type and omics level, identify likely effector genes for osteoarthritis-associated genetic signals and highlight high-value targets for drug development and repurposing. These findings provide insights into disease aetiopathology, and offer translational opportunities in response to the global clinical challenge of osteoarthritis.

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Item Type:	Article
Authors/Creators:	Steinberg, J. Southam, L. Roumeliotis, T.I. Clark, M.J. Jayasuriya, R.L. Swift, D. Shah, K.M. https://orcid.org/0000-0001-9909-6409 Butterfield, N.C. Brooks, R.A. McCaskie, A.W. Bassett, J.H.D. Williams, G.R. Choudhary, J.S. Wilkinson, J.M. https://orcid.org/0000-0001-5577-3674 Zeggini, E.
Copyright, Publisher and Additional Information:	© The Author(s) 2021. 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/.
Dates:	Published: 26 February 2021 Published (online): 26 February 2021 Accepted: 3 February 2021
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Sheffield Teaching Hospitals
Funding Information:	Funder Grant number HELMHOLTZ ZENTRUM MUNCHEN nan
Depositing User:	Symplectic Sheffield
Date Deposited:	18 Mar 2021 14:44
Last Modified:	18 Mar 2021 14:44
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41467-021-21593-7
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:172190

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A molecular quantitative trait locus map for osteoarthritis

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