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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Titill: Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations
Höfundur: arcOGEN consortium
HUNT All-In Pain
ARGO Consortium
Regeneron Genetics Center
Babis, George C
Cheung, Jason Pui Yin
Kang, Jae Hee
Kraft, Peter
Lietman, Steven A
Samartzis, Dino
... 24 fleiri höfundar Sýna alla höfunda
Útgáfa: 2021-09-01
Tungumál: Enska
Umfang: 5368404
Háskóli/Stofnun: Landspitali - The National University Hospital of Iceland
Svið: School of Health Sciences
Health Sciences
Deild: Faculty of Medicine
Faculty of Physical Sciences
Birtist í: Cell; 184(18)
ISSN: 0092-8674
DOI: 10.1016/j.cell.2021.07.038
Efnisorð: Gigtarlæknisfræði; Hjúkrunarstjórnun; drug targets; effector genes; functional genomics; genetic architecture; genome-wide association meta-analysis; osteoarthritis; Slitgigt; Gen; Genome-Wide Association Study; drug targets; effector genes; functional genomics; genetic architecture; genome-wide association meta-analysis; osteoarthritis; Slitgigt; Gen; Osteoarthritis; Genome-Wide Association Study; General Biochemistry,Genetics and Molecular Biology
URI: https://hdl.handle.net/20.500.11815/3768

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Tilvitnun:

arcOGEN consortium , HUNT All-In Pain , ARGO Consortium , Regeneron Genetics Center , Babis , G C , Cheung , J P Y , Kang , J H , Kraft , P , Lietman , S A , Samartzis , D , Slagboom , P E , Stefansson , K , Thorsteinsdottir , U , Tobias , J H , Uitterlinden , A G , Winsvold , B , Zwart , J-A , Davey Smith , G , Sham , P C , Thorleifsson , G , Gaunt , T R , Morris , A P , Valdes , A M , Tsezou , A , Cheah , K S E , Ikegawa , S , Hveem , K , Esko , T , Wilkinson , J M , Meulenbelt , I , Lee , M T M , van Meurs , J B J , Styrkársdóttir , U & Zeggini , E 2021 , ' Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations ' , Cell , vol. 184 , no. 18 , pp. 4784-4818.e17 . https://doi.org/10.1016/j.cell.2021.07.038

Útdráttur:

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Athugasemdir:

Funding Information: T.R.G. and J.Z. receive research funding from GlaxoSmithKline. T.R.G. receives research funding from Biogen. U.S., K.S., L. Stefánsdóttir, G.B., S.H.L., U.T., and G. T. are employed by deCODE genetics/Amgen Inc. A.M.V. is a consultant for Zoe Global Ltd. All other authors report no competing interests. All Regeneron Genetics Center banner authors are current employees and/or stockholders of Regeneron Pharmaceuticals. Funding Information: We thank Nigel W. Rayner and Ahmed Elhakeem for their input. This research was conducted using the UK Biobank Resource under application numbers 9979 and 23359. G.D.S. and T.R.G. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1&4. A.M.V. is funded by the NIHR Nottingham BRC. J.Z. is funded by a Vice-Chancellor Fellowship from the University of Bristol. This research was also funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). Study design and project coordination, E. Zeggini; Writing Group, U.S. J.B.J.v.M. J.M.W. M.T.M.L. K.S.E.C. L.S. C.G.B. K.H. Y.Z. R.C.d.A. L. Stef?nsd?ttir, E. Zeggini, A.P.M. G.T. P.C.S. J.Z. and T.R.G.; Core Analyses, C.G.B. K. Hatzikotoulas, L. Southam, L. Stef?nsd?ttir, Y.Z. R.C.d.A. T.T.W. J.Z. A.H. M.T.-L. and J.M.W.; Individual Study Design and Principal Investigators, E. Zeggini, U.S. J.B.J.v.M. M.T.M.L. I.M. J.M.W. T.E. K. Hveem, S.I. K.S.E.C. A.T. A.M.V. K.S. P.E.S. P.C. G.D.S. J.H.T. T.R.G. S.A.L. G.C.B. A.G.U. U.T. P.K. J.H.K. arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, and Regeneron Genetics Center; Analyses, Genotyping, and Phenotyping in Individual Studies, C.G.B. K.H. L. Southam, J.M.W. L. Stef?nsd?ttir, Y.Z. R.C.d.A. T.T.W. J.Z. A.H. M.T.-L. A.H.S. C.T. E. Zengini, A.B. G.T. G.B. H.J. T.I. R.M. H.T. M.K. M.T. R.R.G.H.H.N. M.M. J.P.Y.C. D.S. J.-A.Z. A.L. M.B.J. L.F.T. B.W. M.E.G. J.S. M.S. G.A. A.G. S.H.L. arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, and Regeneron Genetics Center. All authors contributed to the final version of the manuscript. T.R.G. and J.Z. receive research funding from GlaxoSmithKline. T.R.G. receives research funding from Biogen. U.S. K.S. L. Stef?nsd?ttir, G.B. S.H.L. U.T. and G. T. are employed by deCODE genetics/Amgen Inc. A.M.V. is a consultant for Zoe Global Ltd. All other authors report no competing interests. All Regeneron Genetics Center banner authors are current employees and/or stockholders of Regeneron Pharmaceuticals. Funding Information: We thank Nigel W. Rayner and Ahmed Elhakeem for their input. This research was conducted using the UK Biobank Resource under application numbers 9979 and 23359. G.D.S. and T.R.G. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1&4. A.M.V. is funded by the NIHR Nottingham BRC . J.Z. is funded by a Vice-Chancellor Fellowship from the University of Bristol . This research was also funded by the UK Medical Research Council Integrative Epidemiology Unit ( MC_UU_00011/4 ). Publisher Copyright: © 2021 The Authors Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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