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Boer, C.G.* ; Hatzikotoulas, K. ; Southam, L. ; Stefansdottir, L.* ; Zhang, Y.* ; Coutinho de Almeida, R.* ; Wu, T.T.* ; Zheng, J.* ; Hartley, A.* ; Teder-Laving, M.* ; Skogholt, A.H.* ; Terao, C.* ; Zengini, E.* ; Alexiadis, G.* ; Barysenska, A. ; Bjornsdottir, G.* ; Gabrielsen, M.E.* ; Gilly, A. ; Ingvarsson, T.* ; Johnsen, M.B.* ; Jonsson, H.* ; Kloppenburg, M.* ; Luetge, A.* ; Lund, S.H.* ; Mägi, R.* ; Mangino, M.* ; Nelissen, R.R.G.H.H.* ; Shivakumar, M.* ; Steinberg, J. ; Takuwa, H.* ; Thomas, L.F.* ; Tuerlings, M.* ; 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.* ; Styrkarsdottir, U.* ; Zeggini, E.

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Cell 184, 4784-4818.e17 (2021)
Postprint Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Drug Targets ; Effector Genes ; Functional Genomics ; Genetic Architecture ; Genome-wide Association Meta-analysis ; Osteoarthritis; Genome-wide Association; Vitamin-d Supplementation; Lumbar Disc Degeneration; Low-back-pain; Knee Osteoarthritis; Tenascin-c; Bone Loss; Human Immunodeficiency; Cartilage Volume; Point Mutations
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 184, Issue: 18, Pages: 4784-4818.e17 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Grants UK Medical Research Council Integrative Epidemiology Unit
University of Bristol
NIHR Nottingham BRC
Medical Research Council Integrative Epidemiology Unit at the University of Bristol
UK Biobank Resource