Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations
Cindy G. Boer(Erasmus MC), Konstantinos Hatzikotoulas(Helmholtz Zentrum München), Lorraine Southam(Helmholtz Zentrum München), Lilja Stefánsdóttir(deCODE Genetics (Iceland)), Yanfei Zhang(Geisinger Health System), Rodrigo Coutinho de Almeida(Leiden University Medical Center), Tian Wu(University of Hong Kong), Jie Zheng(University of Bristol), April Hartley(Southmead Hospital), Maris Teder‐Laving(University of Tartu), Anne Heidi Skogholt(Norwegian University of Science and Technology), Chikashi Terao(RIKEN Center for Integrative Medical Sciences), Eleni Zengini(KAT General Hospital of Attica), George Alexiadis(KAT General Hospital of Attica), Andrei Barysenka(Helmholtz Zentrum München), Gyða Björnsdóttir(deCODE Genetics (Iceland)), Maiken E. Gabrielsen(Norwegian University of Science and Technology), Arthur Gilly(Helmholtz Zentrum München), Þorvaldur Ingvarsson(University of Iceland), Marianne Bakke Johnsen(Oslo University Hospital), Helgi Jónsson(University of Iceland), M. Kloppenburg(Leiden University Medical Center), Almut Luetge(Norwegian University of Science and Technology), Sigrún H. Lund(deCODE Genetics (Iceland)), Reedik Mägi(University of Tartu), Massimo Mangino(King's College London), Rob G. H. H. Nelissen(Leiden University Medical Center), Manu Shivakumar(University of Pennsylvania), Julia Steinberg(The University of Sydney), Hiroshi Takuwa(Shimane University), Laurent F. Thomas(Norwegian University of Science and Technology), Margo Tuerlings(Leiden University Medical Center), John Loughlin(National and Kapodistrian University of Athens), Nigel Arden(University of Hong Kong), Fraser Birrell(Brigham and Women's Hospital), Andrew Carr(Harvard University), Panos Deloukas(Geisinger Health System), Michael Doherty(Rush University Medical Center), Andrew W. McCaskie(Leiden University Medical Center), William Ollier(deCODE Genetics (Iceland)), Ashok Rai(deCODE Genetics (Iceland)), Stuart H. Ralston(Southmead Hospital), Tim D. Spector(Erasmus MC), Gillian A. Wallis(Oslo University Hospital), Amy E. Martinsen(Oslo University Hospital), Cristen J. Willer(University of Bristol), Egil A. Fors(University of Hong Kong), Ingunn Mundal(deCODE Genetics (Iceland)), Knut Hagen(University of Bristol), Kristian Bernhard Nilsen(University of Manchester), Marie Udnesseter Lie(University of Nottingham), Sigrid Børte(University of Thessaly), Ben Brumpton(University of Hong Kong), Jonas B. Nielsen(RIKEN Center for Integrative Medical Sciences), Lars G. Fritsche(Norwegian University of Science and Technology), Wei Zhou(University of Tartu), Ingrid Heuch(University of Sheffield), Kjersti Storheim(Leiden University Medical Center), Evangelos Tyrpenou(Institute of Biomedical Sciences, Academia Sinica), A. Koukakis(Erasmus MC), Dimitrios Chytas(deCODE Genetics (Iceland)), Dimitrios Stergios Evangelopoulos(TUM Klinikum), Chronopoulos Efstathios(Oslo University Hospital), Spiros G. Pneumaticos, Vasileios S. Nikolaou, Κonstantinos Ν. Malizos(University of Manchester), Lydia Anastasopoulou, Gonçalo R. Abecasis(Institute of Biomedical Sciences, Academia Sinica), Aris Baras, Michael Cantor, Giovanni Coppola(Helmholtz Zentrum München), Andrew Deubler, Aris N. Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan R. Shuldiner, Katia Karalis, Katherine Siminovitch, Christina Beechert, Caitlin Forsythe(Geisinger Health System), Erin D. Fuller, Zhenhua Gu(Oslo University Hospital), Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla(Leiden University Medical Center), Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Xiaodong Bai, Suganthi Balasubramanian, Boris Boutkov, Gisu Eom, Lukas Habegger(Helmholtz Zentrum München), Alicia Hawes, Olga Krasheninina, Rouel Lanche(deCODE Genetics (Iceland)), Adam J. Mansfield(Institute of Biomedical Sciences, Academia Sinica), Evan K. Maxwell, Mona Nafde(University of Manchester), Sean O’Keeffe(deCODE Genetics (Iceland)), Max Orelus, Razvan Panea, Tommy Polanco, Ayesha Rasool, William Salerno, Jeffrey Staples, Dadong Li, Deepika Sharma, Ilanjana Banerjee, Jonas Bovijn(deCODE Genetics (Iceland)), Adam E. Locke(Institute of Biomedical Sciences, Academia Sinica), Niek Verweij, Mary E. Haas, George Hindy, Tanima De, Parsa Akbari, Olukayode Sosina, Manuel A. R. Ferreira, Marcus B. Jones, Jason Mighty, Michelle G. LeBlanc, Lyndon J. Mitnaul, George C. Babis(Agia Olga Hospital), Jason Pui Yin Cheung(University of Hong Kong), Jae H. Kang(Brigham and Women's Hospital), Peter Kraft(Harvard University), Steven A. Lietman(Geisinger Health System), Dino Samartzis(University of Hong Kong), P. Eline Slagboom(Leiden University Medical Center), Kari Stefansson(deCODE Genetics (Iceland)), Unnur Þorsteinsdóttir(deCODE Genetics (Iceland)), Jonathan H. Tobias(University of Bristol), André G. Uitterlinden(Erasmus MC), Bendik S. Winsvold(Oslo University Hospital), John‐Anker Zwart(Oslo University Hospital), George Davey Smith(University of Bristol), Pak C. Sham(Erasmus MC), Guðmar Þorleifsson(deCODE Genetics (Iceland)), Tom R. Gaunt(University of Bristol), Andrew P. Morris(University of Manchester), Ana M. Valdes(University of Nottingham), Aspasia Tsezou(University of Thessaly), Kathryn S.E. Cheah(University of Hong Kong), Shiro Ikegawa(University of Bristol), Kristian Hveem(University of Nottingham), Tõnu Esko(University of Tartu), J. Mark Wilkinson(University of Sheffield), Ingrid Meulenbelt(Leiden University Medical Center), Ming Ta Michael Lee(Institute of Biomedical Sciences, Academia Sinica), Joyce B. J. van Meurs(Erasmus MC), Unnur Styrkársdóttir(deCODE Genetics (Iceland)), Eleftheria Zeggini(Helmholtz Zentrum München)
Cited by 452Open Access
Abstract
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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