The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Accepted/In Press date: 2 August 2023

e-pub ahead of print date: 22 August 2023

Published date: September 2023

Additional Information: Funding Information: No funders had any role in study design or manuscript writing. BGF is a National Institute of Health and Care Research Academic Clinical Lecturer and was previously supported by a Medical Research Council (MRC) clinical research training fellowship ( MR/S021280/1 ). MF, RE, FS are supported, and this work is funded by a Wellcome Trust collaborative award (reference number 209233 ). ML is supported by a University of Queensland Research Training Scholarship from The University of Queensland (UQ). ML thanks the Commonwealth Scientific and Industrial Research Organisation for the support through a Postgraduate Top-Up Scholarship. CL was funded by the MRC (MR/S00405X/1) as well as a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society ( 223267/Z/21/Z ). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 080280/Z/06/Z , 20378/Z/16/Z , 223267/Z/21/Z ]. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. NCH acknowledges support from the MRC ( MC_PC_21003 ; MC_PC_21001 ) and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton . BGF, MF, AEH, GDS, JHT work in the MRC Integrative Epidemiology Unit at the University of Bristol , which is supported by the MRC (MC_UU_00011/1). JPK is funded by a National Health and Medical Research Council (Australia) Investigator grant ( GNT1177938 ), and by the Lions Medical Research Foundation (2020 Lions Dunning-Orlich Investigator Award). DSE acknowledges funding from NIH / NIA U24AG051129 . The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institute of Health funding from the following institutes: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: R01 AR052000 , K24 AR048841 , U01 AG027810 , U01 AG042124 , U01 AG042139 , U01 AG042140 , U01 AG042143 , U01 AG042145 , U01 AG042168 , U01 AR066160 , and UL1 TR000128 . The Study of Osteoporotic Fractures ( SOF ) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407 , R01 AR3 5582 , R01 AR35583 , R01 AR35584 , R01 AG005394 , R01 AG027574 , and R01 AG027576 . Funding Information: Primarily funded by the Medical Research Council and Wellcome Trust.This work has been conducted using the UK Biobank resource (application number 17295). The authors would like to thank the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RSI & RSII) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The authors would like to thank Pascal Arp, Mila Jhamai, Marijn Verkerk, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Linda Broer PhD, for the creation of the imputed data. No funders had any role in study design or manuscript writing. BGF is a National Institute of Health and Care Research Academic Clinical Lecturer and was previously supported by a Medical Research Council (MRC) clinical research training fellowship (MR/S021280/1). MF, RE, FS are supported, and this work is funded by a Wellcome Trust collaborative award (reference number 209233). ML is supported by a University of Queensland Research Training Scholarship from The University of Queensland (UQ). ML thanks the Commonwealth Scientific and Industrial Research Organisation for the support through a Postgraduate Top-Up Scholarship. CL was funded by the MRC (MR/S00405X/1) as well as a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (223267/Z/21/Z). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 080280/Z/06/Z, 20378/Z/16/Z, 223267/Z/21/Z]. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. NCH acknowledges support from the MRC (MC_PC_21003; MC_PC_21001) and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton. BGF, MF, AEH, GDS, JHT work in the MRC Integrative Epidemiology Unit at the University of Bristol, which is supported by the MRC (MC_UU_00011/1). JPK is funded by a National Health and Medical Research Council (Australia) Investigator grant (GNT1177938), and by the Lions Medical Research Foundation (2020 Lions Dunning-Orlich Investigator Award). DSE acknowledges funding from NIH/NIA U24AG051129. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institute of Health funding from the following institutes: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: R01 AR052000, K24 AR048841, U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR3 5582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. Publisher Copyright: © 2023 The Author(s)

Keywords: Cartilage, Genome-wide association study, Mendelian randomisation, Osteoarthritis

Local EPrints ID: 480989

URI: http://eprints.soton.ac.uk/id/eprint/480989

DOI: doi:10.1016/j.ebiom.2023.104759

ISSN: 2352-3964

PURE UUID: 4d0e9e54-174f-4049-a35f-2af4c81c6420

ORCID for Nicholas Harvey: orcid.org/0000-0002-8194-2512

Date deposited: 14 Aug 2023 16:50

Last modified: 18 Mar 2024 02:59