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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 Forschungsdaten DOI PMC
Open Access Hybrid
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 184, Heft: 18, Seiten: 4784-4818.e17 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506700-001
Förderungen 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
DOI 10.1016/j.cell.2021.07.038
WOS ID WOS:000692441200013
Scopus ID 85114044916
PubMed ID 34450027
Erfassungsdatum 2021-09-27
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